520 results match your criteria Clinical Pharmacology in Drug Development [Journal]


A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects.

Clin Pharmacol Drug Dev 2019 Feb 21. Epub 2019 Feb 21.

Greenwich Biosciences, Inc., Carlsbad, CA, USA.

GW Pharmaceuticals' formulation of highly purified cannabidiol oral solution is approved in the United States for seizures associated with Lennox-Gastaut and Dravet syndromes in patients aged ≥2 years, for which clobazam, stiripentol, and valproate are commonly used antiepileptic drugs. This open-label, fixed-sequence, drug-drug interaction, healthy volunteer trial investigated the impact of cannabidiol on steady-state pharmacokinetics of clobazam (and N-desmethylclobazam), stiripentol, and valproate; the reciprocal effect of clobazam, stiripentol, and valproate on cannabidiol and its major metabolites (7-hydroxy-cannabidiol [7-OH-CBD] and 7-carboxy-cannabidiol [7-COOH-CBD]); and cannabidiol safety and tolerability when coadministered with each antiepileptic drug. Concomitant cannabidiol had little effect on clobazam exposure (maximum concentration [C ] and area under the concentration-time curve [AUC], 1. Read More

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http://dx.doi.org/10.1002/cpdd.665DOI Listing
February 2019

A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery.

Clin Pharmacol Drug Dev 2019 Feb 20. Epub 2019 Feb 20.

Tampa General Hospital, Tampa, FL, USA.

An intravenous (IV) formulation of meloxicam is being studied for moderate to severe pain management. This phase 3, randomized, multicenter, double-blind, placebo-controlled trial evaluated the safety of once-daily meloxicam IV 30 mg in subjects following major elective surgery. Eligible subjects were randomized (3:1) to receive meloxicam IV 30 mg or placebo administered once daily. Read More

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http://dx.doi.org/10.1002/cpdd.666DOI Listing
February 2019

Pharmacokinetics, Food Effect, Ketoconazole Interaction, and Safety of JTK-853, a Novel Nonnucleoside HCV Polymerase Inhibitor, After Ascending Single and Multiple Doses in Healthy Subjects.

Clin Pharmacol Drug Dev 2019 Feb 19. Epub 2019 Feb 19.

Clinical Pharmacology, Akros Pharma Inc., Princeton, NJ, USA.

Pharmacokinetics, safety, and tolerability of JTK-853, a novel HCV polymerase inhibitor, were evaluated in single and multiple ascending dose (SAD, MAD) studies, with food- and ketoconazole-related effects on exposure to JTK-853 and its active (CYP3A4 mediated) metabolite M2. JTK-853 was safe and well tolerated in both studies. In the SAD study, at doses >1600 mg (with standard breakfast [SBF]), JTK-853 exposure did not increase further, was substantially higher (AUC increase: 3- to 8-fold) with SBF (vs fasted), with a moderate increase in AUC (approximately 1. Read More

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http://dx.doi.org/10.1002/cpdd.656DOI Listing
February 2019

The Relative Bioavailability and Effects of Food and Acid-Reducing Agents on Filgotinib Tablets in Healthy Subjects.

Clin Pharmacol Drug Dev 2019 Feb 15. Epub 2019 Feb 15.

Horizon Pharma, Brisbane, CA, USA.

Filgotinib is a potent, selective Janus kinase-1 inhibitor being developed to treat chronic inflammatory diseases. This phase 1 study in healthy subjects evaluated the relative bioavailability of filgotinib maleate tablets versus the reference tablet (filgotinib hydrochloride) and effects of food and acid-reducing agents (ARAs) on the pharmacokinetics of filgotinib and its major metabolite. Noncompartmental pharmacokinetic parameters of filgotinib and its major metabolite were compared between the 2 tablets at 100- and 200-mg doses and with or without food or ARAs. Read More

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http://dx.doi.org/10.1002/cpdd.659DOI Listing
February 2019

Lesinurad: Evaluation of Pharmacokinetic and Pharmacodynamic Interactions With Warfarin in Healthy Volunteers.

Clin Pharmacol Drug Dev 2019 Feb 13. Epub 2019 Feb 13.

AstraZeneca, Gaithersburg, MD, USA.

Lesinurad is a selective uric acid reabsorption inhibitor approved for use in combination with xanthine oxidase inhibitors for the treatment of hyperuricemia associated with gout. In vitro, lesinurad was shown to be a weak inhibitor of cytochrome P450 (CYP)2C9 and a weak inducer of CYP3A4. Warfarin is a widely prescribed oral coumarin-based anticoagulant commonly prescribed in gout patients. Read More

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http://dx.doi.org/10.1002/cpdd.662DOI Listing
February 2019
1 Read

Effects of Food and Antacids on Pharmacokinetics and Pharmacodynamics of Lesinurad, a Selective Urate Reabsorption Inhibitor.

Clin Pharmacol Drug Dev 2019 Feb 12. Epub 2019 Feb 12.

AstraZeneca, Gaithersburg, MD, USA.

Two clinical studies were performed in healthy volunteers to investigate food and antacid effects on lesinurad, a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. Study 1 evaluated a high-fat, high-calorie meal or high doses of antacids (3000 mg calcium carbonate or 1600 mg magnesium hydroxide/1600 mg aluminum hydroxide) on the pharmacokinetics (PK) and pharmacodynamics (PD) of 400 mg oral lesinurad. Study 2 evaluated low doses of antacids (1250 mg calcium carbonate or 800 mg magnesium hydroxide/800 mg aluminum hydroxide) on the PK and PD of 400 mg lesinurad. Read More

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http://dx.doi.org/10.1002/cpdd.663DOI Listing
February 2019
1 Read

A Cocktail Interaction Study Evaluating the Drug-Drug Interaction Potential of the Perpetrator Drug ASP8477 at Multiple Ascending Dose Levels.

Clin Pharmacol Drug Dev 2019 Feb 7. Epub 2019 Feb 7.

Department of Clinical Pharmacology and Exploratory Development, Astellas Pharma Europe BV, Leiden, The Netherlands.

ASP8477 (molecular weight 325.36 g/mol) is a fatty acid amide hydrolase inhibitor intended for the treatment of neuropathic pain. Results from in vitro studies indicated that ASP8477 is a direct inhibitor of cytochrome P450 (CYP) 2C8, 2C9, 2C19, 2D6, and 3A4 enzymes at expected efficacious concentrations, with the strongest effect on CYP2C19; a phase 1 study confirmed ASP8477 to be a CYP2C19 inhibitor. Read More

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http://dx.doi.org/10.1002/cpdd.660DOI Listing
February 2019
1 Read

Designer Benzodiazepines: A Review of Published Data and Public Health Significance.

Clin Pharmacol Drug Dev 2019 Feb 7. Epub 2019 Feb 7.

Tufts University School of Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1002/cpdd.667DOI Listing
February 2019

2018 CPDD Peer Reviewers.

Authors:

Clin Pharmacol Drug Dev 2019 Feb;8(2):260

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http://dx.doi.org/10.1002/cpdd.661DOI Listing
February 2019

Randomized Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Topical Daprodustat in Healthy Volunteers and in Patients With Diabetic Foot Ulcers.

Clin Pharmacol Drug Dev 2019 Feb 5. Epub 2019 Feb 5.

University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.

Daprodustat, a small-molecule inhibitor of prolyl hydroxylases, prevents breakdown of hypoxia-inducible factor (HIF), leading to increased transcription of HIF-responsive genes. This randomized, placebo-controlled study evaluated the safety, tolerability, and pharmacokinetics of a topical formulation of daprodustat in healthy volunteers (intact skin) and in patients with diabetic foot ulcers (DFUs) following single and/or 14-day repeat-dose administration. In the diabetic patients, exploratory assessments of wound area, volume, and depth were made to qualitatively assess effectiveness. Read More

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http://dx.doi.org/10.1002/cpdd.654DOI Listing
February 2019
4 Reads

Use of Population Pharmacokinetic Analyses Among FDA-Approved Biologics.

Clin Pharmacol Drug Dev 2019 Feb 1. Epub 2019 Feb 1.

Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Biologics, especially monoclonal antibodies, are increasingly important in the pharmaceutical marketplace. Population pharmacokinetic (PK) analyses could be useful to guide the need for dose adjustments among special populations, yet it is unknown how commonly such analyses are performed during biologics development. We summarized the characteristics of population PK models of biologics and examined their role in informing the drug labels. Read More

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http://doi.wiley.com/10.1002/cpdd.658
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http://dx.doi.org/10.1002/cpdd.658DOI Listing
February 2019
2 Reads

Influence of Renal Function on Evolocumab Exposure, Pharmacodynamics, and Safety.

Clin Pharmacol Drug Dev 2019 Jan 24. Epub 2019 Jan 24.

Amgen Inc., Thousand Oaks, CA, USA.

We evaluated the pharmacokinetics, pharmacodynamics, and safety of evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), in an open-label, parallel-design study in participants with normal renal function (n = 6), severe renal impairment (RI; n = 6), or end-stage renal disease (ESRD) receiving hemodialysis (n = 6) who received a single 140-mg dose of evolocumab. The effects of evolocumab treatment on low-density lipoprotein cholesterol (LDL-C) lowering and unbound PCSK9 concentrations were similar in the normal renal function group and the renally impaired groups. Geometric mean C and AUC values in the severe RI and ESRD hemodialysis groups compared with the normal renal function group were lower but within 37% of the normal renal function group (Jonckheere-Terpstra trend test; C , P = . Read More

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http://dx.doi.org/10.1002/cpdd.650DOI Listing
January 2019
1 Read

Exposure-Response Analysis for Efficacy of Daclatasvir, Asunaprevir, and Beclabuvir Combinations in HCV-Infected Patients.

Clin Pharmacol Drug Dev 2019 Jan 22. Epub 2019 Jan 22.

Bristol-Myers Squibb Research and Development, Lawrenceville, NJ, USA.

The combination regimen of daclatasvir, asunaprevir, and beclabuvir (3DAA regimen) was developed as a fixed-dose combination for the treatment of hepatitis C virus (HCV) infection in Japan. The objectives of this analysis were to characterize the relationship between drug exposure and sustained virologic response at posttreatment week 12 (SVR12) in HCV-infected subjects and to evaluate the impact of demographic covariates and clinical factors on the exposure-response (E-R) relationship. The E-R efficacy analysis was performed with data from phase 2 and phase 3 studies in HCV-infected subjects treated with the 3DAA regimen. Read More

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http://dx.doi.org/10.1002/cpdd.646DOI Listing
January 2019

Pharmacokinetics of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules in De Novo Liver Transplant.

Clin Pharmacol Drug Dev 2019 Jan 22. Epub 2019 Jan 22.

Veloxis Pharmaceuticals, Inc., Cary, NC, USA.

The pharmacokinetics of once-daily extended-release tacrolimus tablets (LCPT) in de novo liver transplantation have not been previously reported. In this phase II, randomized, open-label study, de novo liver transplant recipients were randomized to LCPT 0.07-0. Read More

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http://dx.doi.org/10.1002/cpdd.657DOI Listing
January 2019
2 Reads

Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of ELX-02, a Potential Treatment for Genetic Disorders Caused by Nonsense Mutations, in Healthy Volunteers.

Clin Pharmacol Drug Dev 2019 Jan 16. Epub 2019 Jan 16.

SGS Life Sciences, Clinical Pharmacology Unit, Antwerp, Belgium.

ELX-02 is an investigational synthetic eukaryotic ribosome-selective glycoside optimized as a translational read-through molecule that induces read through of nonsense mutations, resulting in normally localized full-length functional proteins. ELX-02 is being developed as a therapy for genetic diseases caused by nonsense mutations. Two phase 1a, randomized, double-blind placebo-controlled, single-ascending-dose studies were conducted in healthy human subjects to evaluate the safety and pharmacokinetics of ELX-02. Read More

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http://dx.doi.org/10.1002/cpdd.647DOI Listing
January 2019
2 Reads

A Phase 1 Study of Intravenous Plazomicin in Healthy Adults to Assess Potential Effects on the QT/QTc Interval, Safety, and Pharmacokinetics.

Clin Pharmacol Drug Dev 2019 Jan 16. Epub 2019 Jan 16.

Achaogen, Inc, South San Francisco, CA, USA.

Plazomicin is an aminoglycoside with in vitro activity against multidrug-resistant Enterobacteriaceae. A phase 1, randomized, double-blind, crossover study assessed the potential effects of plazomicin on cardiac repolarization (NCT01514929). Fifty-six healthy adults (24 men, 32 women) received a single therapeutic dose of plazomicin (15 mg/kg administered by 30-minute intravenous infusion), a single supratherapeutic dose of plazomicin (20 mg/kg administered by 30-minute intravenous infusion), placebo, or oral moxifloxacin (400 mg). Read More

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http://dx.doi.org/10.1002/cpdd.653DOI Listing
January 2019
2 Reads

A Phase 1b Trial to Assess the Pharmacokinetics of Ezutromid in Pediatric Duchenne Muscular Dystrophy Patients on a Balanced Diet.

Clin Pharmacol Drug Dev 2019 Jan 16. Epub 2019 Jan 16.

Summit Therapeutics, Abingdon, UK.

Ezutromid (SMT C1100) is a small-molecule utrophin modulator that was developed to treat Duchenne muscular dystrophy (DMD). Previous clinical trials of this agent revealed lower exposure in DMD patients compared with healthy volunteers, which may reflect differences in diet. This study evaluated the pharmacokinetics of ezutromid in patients with DMD who followed a balanced diet. Read More

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http://dx.doi.org/10.1002/cpdd.642DOI Listing
January 2019
1 Read

A Phase 1 Randomized, Placebo-Controlled Trial With a Topical Inhibitor of Stearoyl-Coenzyme A Desaturase 1 Under Occluded and Nonoccluded Conditions.

Clin Pharmacol Drug Dev 2019 Jan 16. Epub 2019 Jan 16.

CMAX, a division of IDT Australia Limited, Adelaide, South Australia, Australia.

Stearoyl-coenzyme A desaturase 1 (SCD-1) in sebaceous glands is a key enzyme in the synthesis of monounsaturated fatty acids essential for acne development. GSK1940029 gel, a novel SCD-1 inhibitor, is being developed as a potential treatment for acne. To assess the irritation potential, pharmacokinetics (PK), and safety of topical GSK1940029 to the skin of healthy adults, two interdependent studies were conducted in parallel. Read More

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http://dx.doi.org/10.1002/cpdd.644DOI Listing
January 2019
2 Reads

Ataluren Pharmacokinetics in Healthy Japanese and Caucasian Subjects.

Clin Pharmacol Drug Dev 2019 Feb 10;8(2):172-178. Epub 2019 Jan 10.

PTC Therapeutics, Inc, South Plainfield, NJ, USA.

To evaluate the potential for ethnicity-related differences in ataluren pharmacokinetics (PK) and safety, a phase 1 single-dose study was conducted in 48 healthy (24 Japanese and 24 Caucasian subjects), nonsmoking male volunteers who were equally divided into 3 cohorts of oral doses at 5, 10, and 20 mg/kg. Blood samples were collected until 48 hours postdose. PK results demonstrated rapid absorption of ataluren, with peak plasma levels (C ) being attained between 0. Read More

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http://dx.doi.org/10.1002/cpdd.645DOI Listing
February 2019
2 Reads

Population Pharmacokinetic Analysis of Daclatasvir, Asunaprevir, and Beclabuvir Combination in HCV-Infected Subjects.

Clin Pharmacol Drug Dev 2019 Jan 10. Epub 2019 Jan 10.

Bristol-Myers Squibb, Princeton, NJ, USA.

A fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor) was approved for hepatitis C virus treatment in Japan. The objectives of the analyses were to develop the daclatasvir, asunaprevir, and beclabuvir population pharmacokinetic models for the combination regimen. First, an original population pharmacokinetic model was developed using the data in non-Japanese hepatitis C virus-infected subjects. Read More

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http://dx.doi.org/10.1002/cpdd.649DOI Listing
January 2019
5 Reads

An Open-Label, Randomized, Pivotal Bioequivalence Study of Oral Rolapitant.

Clin Pharmacol Drug Dev 2019 Feb 9;8(2):152-159. Epub 2019 Jan 9.

TESARO, Inc., Waltham, MA, USA.

Rolapitant, a selective and long-acting neurokinin-1 receptor antagonist, is approved in an oral formulation for prevention of delayed chemotherapy-induced nausea and vomiting in adults. This pivotal open-label, randomized, single-dose, multicenter, parallel-group study assessed the bioequivalence of a single oral dose of 180 mg of rolapitant administered in tablet (2 × 90-mg tablets) or capsule (4 × 45-mg capsules) form in healthy male and female subjects. Blood samples for pharmacokinetic analysis were collected predose and at times up to 912 hours postdose. Read More

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http://doi.wiley.com/10.1002/cpdd.651
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http://dx.doi.org/10.1002/cpdd.651DOI Listing
February 2019
15 Reads

No Effect of Plazomicin on the Pharmacokinetics of Metformin in Healthy Subjects.

Clin Pharmacol Drug Dev 2019 Jan 3. Epub 2019 Jan 3.

Achaogen, Inc., South San Francisco, CA, USA.

Plazomicin is an aminoglycoside that was engineered to overcome aminoglycoside-modifying enzymes, which are the most common aminoglycoside resistance mechanism in Enterobacteriaceae. Because plazomicin is predominantly eliminated via renal pathways, an in vitro study was conducted to determine whether plazomicin inhibits the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion (MATE1 and MATE2-K) transporters, using metformin as a probe substrate. Plazomicin inhibited OCT2, MATE1, and MATE2-K transporters with half-maximal inhibition of the transporter values of 5120, 1300, and 338 μg/mL, respectively. Read More

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http://dx.doi.org/10.1002/cpdd.648DOI Listing
January 2019
1 Read

Ketoconazole and Liver Injury: A Five-Year Update.

Clin Pharmacol Drug Dev 2019 Jan;8(1):6-8

Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.

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http://doi.wiley.com/10.1002/cpdd.652
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http://dx.doi.org/10.1002/cpdd.652DOI Listing
January 2019
2 Reads

Quantitative Assessment of the Effect of Chronic Kidney Disease on the Nonrenal Clearance of 10 Drugs After Intravenous Administration.

Clin Pharmacol Drug Dev 2019 Feb 27;8(2):138-151. Epub 2018 Dec 27.

Department of Pharmaceutics, University of Florida, Gainesville, FL, USA.

The investigation identified 10 publications that reported the individual values of total clearance (CL), renal clearance (CLr), nonrenal clearance (CLnr), and the glomerular filtration rate (GFR), in subjects with varying renal functions. We used these data to estimate extent and prevalence of changes in CLnr in chronic kidney disease (CKD) by examining the relationship between clearances and renal function. The investigation was restricted to drugs given intravenously and eliminated by mixed renal and nonrenal pathways. Read More

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http://dx.doi.org/10.1002/cpdd.635DOI Listing
February 2019
2 Reads

The Effect of a High-Fat Meal on the Pharmacokinetics of Brigatinib, an Oral Anaplastic Lymphoma Kinase Inhibitor, in Healthy Volunteers.

Clin Pharmacol Drug Dev 2018 Dec 20. Epub 2018 Dec 20.

ARIAD Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.

Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, received accelerated approval in the United States for the treatment of patients with metastatic ALK non-small-cell lung cancer who have progressed on or are intolerant to crizotinib. A clinical study was conducted to assess the effect of food on brigatinib pharmacokinetics (PK). Healthy subjects received a single oral dose of brigatinib 180 mg (2 × 90-mg tablets) after a 10-hour fast or after a high-fat meal in a 2-period, 2-sequence crossover study. Read More

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http://doi.wiley.com/10.1002/cpdd.641
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http://dx.doi.org/10.1002/cpdd.641DOI Listing
December 2018
8 Reads

Elagolix Pharmacokinetic Profiles in Women With Renal or Hepatic Impairment.

Clin Pharmacol Drug Dev 2018 Dec 20. Epub 2018 Dec 20.

Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA.

The aim of these studies was to assess the safety and pharmacokinetics of elagolix, an oral nonpeptide gonadotropin-releasing hormone antagonist following oral administration in women with renal or hepatic impairment. Two phase 1 studies were conducted in adult women with normal renal function versus renal impairment (reduced study), and normal hepatic function versus hepatic impairment (full study design). All women received a single dose of elagolix 200 mg (renal) or 150 mg (hepatic). Read More

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http://doi.wiley.com/10.1002/cpdd.640
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http://dx.doi.org/10.1002/cpdd.640DOI Listing
December 2018
18 Reads

Effect of Rifampicin on the Pharmacokinetics of a Single Dose of Vemurafenib in Patients With BRAF Mutation-Positive Metastatic Malignancy.

Clin Pharmacol Drug Dev 2018 Dec 20. Epub 2018 Dec 20.

Genentech, Inc., South San Francisco, CA, USA.

Vemurafenib prolongs survival in patients with BRAF -mutated advanced melanoma. In vitro studies show cytochrome P450 (CYP) 3A4 is involved in vemurafenib metabolism, but the effect of strong inducers or inhibitors of CYP3A4 on vemurafenib exposure in vivo is unknown. This phase 1, open-label, multicenter study evaluated the effect of rifampicin, a CYP3A4 inducer, on the pharmacokinetics of single-dose vemurafenib in 27 patients with BRAF mutation-positive metastatic malignancy. Read More

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http://dx.doi.org/10.1002/cpdd.643DOI Listing
December 2018
4 Reads

Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous Dose of Miridesap in Healthy Japanese Subjects.

Clin Pharmacol Drug Dev 2018 Dec 17. Epub 2018 Dec 17.

Medicines Development, Japan Development Division, GlaxoSmithKline K.K., Tokyo, Japan.

This phase 1 study characterized the safety, tolerability, pharmacokinetics, and pharmacodynamics of miridesap (GSK2315698) following an intravenous (IV) infusion in healthy Japanese men. Subjects in Cohort 1 received 1-hour IV infusions of 10, 20, and 40 mg of miridesap or placebo, and subjects in Cohort 2 received a 15-hour IV infusion of 20 mg/h of miridesap or placebo. No treatment-related adverse events were reported. Read More

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http://doi.wiley.com/10.1002/cpdd.631
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http://dx.doi.org/10.1002/cpdd.631DOI Listing
December 2018
4 Reads

Single-Dose Pharmacokinetic Properties and Relative Bioavailability of Different Formulations of Posaconazole Oral Suspension in Healthy Volunteers.

Clin Pharmacol Drug Dev 2018 Dec 10. Epub 2018 Dec 10.

University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.

The rate and extent of absorption of drugs belonging to Biopharmaceutics Classification System class II are rate-limited by dissolution and highly dependent on the performance of the formulated product. The purpose of the present study was to investigate the potential impact of a surfactant and the particle size of the active substance on the in vitro drug dissolution profiles and in vivo pharmacokinetics of the poorly soluble drug posaconazole. A comparative physicochemical evaluation was conducted, and 3 formulations of posaconazole oral suspension were tested in various dissolution media compared with the reference product. Read More

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http://dx.doi.org/10.1002/cpdd.636DOI Listing
December 2018
5 Reads

Pharmacokinetics, Safety, and Tolerability Evaluation of Single and Multiple Doses of GSK3342830 in Healthy Volunteers.

Clin Pharmacol Drug Dev 2018 Dec 10. Epub 2018 Dec 10.

GlaxoSmithKline, Clinical Pharmacology Modeling & Simulation, Collegeville, PA, USA.

This was a first-time-in-human randomized, double-blind, single-center, placebo-controlled dose-escalation study to determine the safety, tolerability, and pharmacokinetic (PK) profiles of GSK3342830 after single and repeat intravenous doses in healthy adult subjects (NCT0271424). Sixty-two subjects were enrolled: 48 subjects in part 1 (single dose) and 14 subjects in part 2 (multiple doses). Following single intravenous infusions, total systemic exposure of GSK3342830 was dose proportional over the 250- to 6000-mg dose range evaluated, whereas peak exposure was approximately dose proportional over the dose range. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cpdd.637
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http://dx.doi.org/10.1002/cpdd.637DOI Listing
December 2018
8 Reads

Impact of Splitting or Crushing on the Relative Bioavailability of the Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen.

Clin Pharmacol Drug Dev 2018 Dec 3. Epub 2018 Dec 3.

Janssen Research & Development, Beerse, Belgium.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is an oral once-daily single-tablet regimen for the treatment of human immunodeficiency virus-1 infection. Different administration modalities for the D/C/F/TAF fixed-dose combination tablet were explored in this phase 1 randomized, open-label, 3-period, 3-treatment crossover study enrolling 30 healthy adults. The primary objective was to assess the relative bioavailability of each component after a single dose of D/C/F/TAF (800/150/200/10 mg) administered as a split or crushed tablet (tests) versus swallowed whole (reference). Read More

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http://dx.doi.org/10.1002/cpdd.632DOI Listing
December 2018
4 Reads

Effects of Rifamycin Coadministration on Bedaquiline Desmethylation in Healthy Adult Volunteers.

Clin Pharmacol Drug Dev 2018 Nov 30. Epub 2018 Nov 30.

Department of Pediatrics, University of Toledo College of Medicine, Toledo, OH, USA.

There is an urgent need to identify safe and effective combination treatments for multidrug-resistant (MDR) Mycobacterium tuberculosis infection (TB). Bedaquiline, a new diarylquinoline, is approved for the treatment of MDR pulmonary TB in combination with other drugs, which could include rifabutin, which is also used to treat drug-resistant TB. Both rifabutin and bedaquiline are metabolized via cytochrome P450 3A4, and rifabutin is an inducer of this enzyme. Read More

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http://dx.doi.org/10.1002/cpdd.639DOI Listing
November 2018
3 Reads

Toward Dynamic Prescribing Information: Codevelopment of Companion Model-Informed Precision Dosing Tools in Drug Development.

Clin Pharmacol Drug Dev 2018 Nov 30. Epub 2018 Nov 30.

Certara, Princeton, NJ, USA.

Model-informed precision dosing (MIPD) is biosimulation in healthcare to predict the drug dose for a given patient based on their individual characteristics that is most likely to improve efficacy and/or lower toxicity compared with traditional dosing. Despite widespread use of biosimulation in drug development, MIPD has not been adopted beyond academic-hospital centers. A reason for this is that MIPD requires more supporting evidence in the language that everyday doctors understand-evidence-based medicine. Read More

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http://dx.doi.org/10.1002/cpdd.638DOI Listing
November 2018
3 Reads

Pharmacokinetic Interaction Study Between Saxagliptin and Omeprazole, Famotidine, or Magnesium and Aluminum Hydroxides Plus Simethicone in Healthy Subjects: An Open-Label Randomized Crossover Study.

Clin Pharmacol Drug Dev 2018 Nov 30. Epub 2018 Nov 30.

Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gaithersburg, MD, USA.

Saxagliptin is an orally administered, highly potent, and selective dipeptidyl peptidase-4 inhibitor for the management of type 2 diabetes mellitus. This study was conducted to determine the effect of magnesium and aluminum hydroxides plus simethicone, famotidine, and omeprazole on the pharmacokinetics of saxagliptin and its active metabolite, 5-hydroxy saxagliptin. This was an open-label, randomized, 5-treatment, 5-period, 3-way crossover study in 15 healthy subjects. Read More

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http://dx.doi.org/10.1002/cpdd.634DOI Listing
November 2018
8 Reads

Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction-Results of the CHIARA MIA 1 Trial.

Clin Pharmacol Drug Dev 2018 Nov 19. Epub 2018 Nov 19.

Division of Cardiology 1, Papa Giovanni XXIII Hospital, Bergamo, Italy.

The chymase inhibitor fulacimstat is developed as a first-in-class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo-controlled study was performed in clinically stable patients (40-79 years of age, left ventricular ejection fraction ≤ 45% because of MI in medical history) who were on stable evidence-based standard-of-care therapies for LVD post-MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Read More

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http://doi.wiley.com/10.1002/cpdd.633
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http://dx.doi.org/10.1002/cpdd.633DOI Listing
November 2018
10 Reads

Pharmacokinetics of Single and Repeat Doses of Fluticasone Furoate/Umeclidinium/Vilanterol in Healthy Chinese Adults.

Clin Pharmacol Drug Dev 2018 Nov 14. Epub 2018 Nov 14.

Research and Development, GSK, Pudong Xinqu, Shanghai, China.

The pharmacokinetics (PK) and safety of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) after single and repeat dosing in healthy Chinese adults were assessed. In this open-label study (NCT02837380), subjects received once-daily FF/UMEC/VI 100/62.5/25 μg on day 1 and repeat doses on days 2-7. Read More

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http://dx.doi.org/10.1002/cpdd.626DOI Listing
November 2018
3 Reads

Effect of Food on the Pharmacokinetics of Ertugliflozin and Its Fixed-Dose Combinations Ertugliflozin/Sitagliptin and Ertugliflozin/Metformin.

Clin Pharmacol Drug Dev 2018 Nov 14. Epub 2018 Nov 14.

Pfizer Inc., Groton, CT, USA.

Ertugliflozin, an inhibitor of sodium-glucose cotransporter 2, is approved in the United States and European Union for the treatment of type 2 diabetes in adults, both as monotherapy and as part of fixed-dose combination (FDC) therapies with either sitagliptin or immediate-release metformin. The effect of a standard, high-fat breakfast on the pharmacokinetics of the highest strengths of ertugliflozin monotherapy (15 mg), ertugliflozin/sitagliptin FDC (15-/100-mg), and ertugliflozin/metformin FDC (7.5-/1000-mg) tablets was evaluated. Read More

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http://doi.wiley.com/10.1002/cpdd.629
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http://dx.doi.org/10.1002/cpdd.629DOI Listing
November 2018
9 Reads

A Randomized, Placebo-Controlled, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Soluble Guanylate Cyclase Stimulator Praliciguat in Healthy Subjects.

Clin Pharmacol Drug Dev 2018 Nov 13. Epub 2018 Nov 13.

Ironwood Pharmaceuticals Inc., Cambridge, MA, USA.

Nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling is central to the regulation of several physiological processes, including blood flow and inflammation. Deficient NO signaling is implicated in multiple diseases. sGC stimulators are small molecules that enhance sGC activity, particularly in combination with NO. Read More

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http://doi.wiley.com/10.1002/cpdd.627
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http://dx.doi.org/10.1002/cpdd.627DOI Listing
November 2018
23 Reads

An Open-Label, Single-Dose, Human Mass Balance Study of Amenamevir in Healthy Male Adults.

Clin Pharmacol Drug Dev 2018 Nov 9. Epub 2018 Nov 9.

Astellas Pharma Inc., Tokyo, Japan.

Amenamevir is an inhibitor of the helicase-primase enzyme complex developed for the treatment of varicella zoster virus. This mass balance study investigated the absorption, metabolism, and excretion of a single dose (200 mg) of C-labeled amenamevir in healthy male volunteers. Blood, urine, and feces samples were collected for up to 8 days after the dose. Read More

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http://doi.wiley.com/10.1002/cpdd.630
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http://dx.doi.org/10.1002/cpdd.630DOI Listing
November 2018
28 Reads

Bioequivalence of the Once-Daily Single-Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability.

Clin Pharmacol Drug Dev 2018 Nov 9. Epub 2018 Nov 9.

Janssen Pharmaceutica NV, Beerse, Belgium.

The effect of food on the bioavailability of the components of the once-daily, single-tablet human immunodeficiency virus (HIV) type 1 regimen containing darunavir (DRV 800 mg), cobicistat (COBI 150 mg), emtricitabine (FTC 200 mg), and tenofovir alafenamide (TAF 10 mg) (D/C/F/TAF) (NCT02475135) and the bioequivalence of D/C/F/TAF versus combined intake of the separate agents (NCT02578550) were evaluated. These were 2 phase 1, open-label, randomized, 2-period crossover studies (7-day washout between treatments) in HIV-negative healthy volunteers. Twenty-four participants each received a single dose of D/C/F/TAF in fasted conditions (test) or after a standardized high-fat breakfast (reference). Read More

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http://dx.doi.org/10.1002/cpdd.628DOI Listing
November 2018
10 Reads

Pharmacokinetics of a Lobeglitazone/Metformin Fixed-Dose Combination Tablet (CKD-395 0.5/1000 mg) Versus Concomitant Administration of Single Agents and the Effect of Food on the Metabolism of CKD-395 in Healthy Male Subjects.

Clin Pharmacol Drug Dev 2018 Oct 17. Epub 2018 Oct 17.

Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.

This study aimed to compare the pharmacokinetic profile of combined CKD-395 0.5/1000 mg treatment with that of the coadministration of lobeglitazone sulfate 0.5 mg and metformin hydrochloride (HCl) extended-release (XR) 1000 mg and assess the effect of food on the pharmacokinetics of CKD-395 0. Read More

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http://dx.doi.org/10.1002/cpdd.625DOI Listing
October 2018
1 Read

Bioequivalence of Sarpogrelate in Healthy Chinese Subjects Under Fasting and Fed Conditions: A 4-Way Replicate Crossover Investigation by a Reference-Scaled Average Bioequivalence Approach.

Clin Pharmacol Drug Dev 2018 Oct 16. Epub 2018 Oct 16.

Phase 1 Clinical Unit, China-Frontage USA, First Hospital, Jilin University, Changchun, Jilin, China.

Sarpogrelate is widely used to treat peripheral vascular disorders. However, it has been demonstrated to have a poor pharmacokinetic (PK) profile and marked within-subject variability. Here, the bioequivalence of 2 formulations of sarpogrelate (100-mg tablets) was assessed by using the reference-scaled average bioequivalence (RSABE) method, and the PK parameters were quantified in healthy Chinese subjects under fasting (n = 38) and fed (n = 35) conditions. Read More

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http://doi.wiley.com/10.1002/cpdd.624
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http://dx.doi.org/10.1002/cpdd.624DOI Listing
October 2018
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Pharmacokinetics of Tenofovir Alafenamide, Tenofovir, and Emtricitabine Following Administration of Coformulated Emtricitabine/Tenofovir Alafenamide in Healthy Japanese Subjects.

Clin Pharmacol Drug Dev 2018 Oct 16. Epub 2018 Oct 16.

SOUSEIKAI Sumida Hospital, Tokyo, Japan.

A fixed-dose combination of tenofovir alafenamide (TAF) and emtricitabine (FTC) is available in 2 tablet strengths in Japan (FTC/TAF 200/10 mg and FTC/TAF 200/25 mg). These are used once daily in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 infection. The primary objective of this study was to investigate if there is any clinically relevant pharmacokinetic difference for TAF, tenofovir (TFV), and FTC between Japanese and non-Japanese with historical data. Read More

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http://dx.doi.org/10.1002/cpdd.623DOI Listing
October 2018
5 Reads

A Randomized, Open-Label, Crossover Phase 1 Study to Evaluate the Effects of Food on the Pharmacokinetics of a Single Oral Dose of a 15-mg Tylerdipine Tablet in Healthy Chinese Male Volunteers.

Clin Pharmacol Drug Dev 2019 Jan 10;8(1):126-132. Epub 2018 Oct 10.

Phase 1 Clinical Trial Unit, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Tylerdipine hydrochloride is a novel L-type and T-type dual calcium channel antagonist that has the potential effects of expanding blood vessels and lowering blood pressure. It is expected to reduce the side effect of ankle edema observed with other drugs in the same class. A randomized, open-label, crossover phase 1 study was performed to evaluate the effect of food on the bioavailability of tylerdipine. Read More

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http://doi.wiley.com/10.1002/cpdd.622
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http://dx.doi.org/10.1002/cpdd.622DOI Listing
January 2019
5 Reads

Evaluation of the Safety, Tolerability, and Pharmacokinetics of GSK2269557 (Nemiralisib) Administered Via Dry Powder Inhaler to Healthy Japanese Subjects.

Clin Pharmacol Drug Dev 2019 Jan 10;8(1):78-86. Epub 2018 Oct 10.

Medicines Development, Japan Development Division, GlaxoSmithKline K.K., Tokyo, Japan.

The aim of the study was to assess the safety, tolerability, and pharmacokinetics of single and repeat doses of nemiralisib administered via a dry powder inhaler to healthy Japanese subjects. This was a single-center, double-blind, randomized, placebo-controlled, parallel, single- and repeat-ascending-dose study. Thirty-six healthy Japanese male subjects were randomized to receive either 1 dose strength of nemiralisib or placebo. Read More

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http://dx.doi.org/10.1002/cpdd.614DOI Listing
January 2019
2 Reads

First-in-Human Studies for a Selective RET Tyrosine Kinase Inhibitor, GSK3179106, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers.

Clin Pharmacol Drug Dev 2019 Feb 13;8(2):234-245. Epub 2018 Sep 13.

CMAX Clinical Research Pty Ltd, Royal Adelaide Hospital, Adelaide, South Australia.

Rearranged during transfection (RET), a neuronal growth factor receptor tyrosine kinase, regulates the development of the sympathetic, parasympathetic, motor, and sensory neurons in the enteric nervous system. GSK3179106 is a RET kinase inhibitor that was administered in double-blind, randomized, placebo-controlled single-dose and repeat-dose studies in healthy subjects to investigate its pharmacokinetics and safety/tolerability. In the single-dose study (n = 16), GSK3179106 was dosed from 10 mg to 800 mg, including a food effect arm. Read More

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http://doi.wiley.com/10.1002/cpdd.600
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http://dx.doi.org/10.1002/cpdd.600DOI Listing
February 2019
14 Reads

Distribution, Metabolism, and Excretion of Gedatolisib in Healthy Male Volunteers After a Single Intravenous Infusion.

Clin Pharmacol Drug Dev 2019 Jan 26;8(1):22-31. Epub 2018 Sep 26.

Pfizer Oncology, San Diego, CA, USA.

In this open-label study (NCT02142920), we investigated the distribution, pharmacokinetics, and metabolism of the pan-class-I isoform phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor gedatolisib (PF-05212384), following a single intravenous administration in healthy male subjects. A single, 89-mg, intravenous dose of gedatolisib was associated with a favorable safety profile in the 6 healthy subjects evaluated. Peak plasma concentrations for unchanged gedatolisib and total radioactivity were observed at the end of the 30-minute infusion. Read More

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http://dx.doi.org/10.1002/cpdd.615DOI Listing
January 2019
5 Reads

A Phase 1 Assessment of the QT Interval in Healthy Adults Following Exposure to Rolapitant, a Cancer Supportive Care Antiemetic.

Clin Pharmacol Drug Dev 2018 Sep 26. Epub 2018 Sep 26.

TESARO, Waltham, MA, USA.

This 2-part study evaluated the QT/QTc prolongation potential and safety and pharmacokinetics of the antiemetic rolapitant, a neurokinin-1 receptor antagonist. Part 1 was a randomized, placebo-controlled single-dose-escalation study assessing the safety of a single high dose of rolapitant. Part 2 was a randomized, placebo- and positive-controlled, double-blind parallel-group study including 4 treatment arms: rolapitant at the highest safe dose established in part 1, placebo, moxifloxacin 400 mg (positive control), and rolapitant at the presumed therapeutic dose (180 mg). Read More

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http://dx.doi.org/10.1002/cpdd.619DOI Listing
September 2018
6 Reads

Pharmacokinetics and Safety of CSL112 (Apolipoprotein A-I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function.

Clin Pharmacol Drug Dev 2018 Sep 21. Epub 2018 Sep 21.

CSL Behring, King of Prussia, PA, USA.

CSL112 (Apolipoprotein A-I [human]) is an intravenous preparation of apolipoprotein A-I (apoA-I), formulated with phosphatidylcholine (PC) and stabilized with sucrose, in development to prevent early recurrent cardiovascular events following acute myocardial infarction (AMI). This phase 1 study was designed to determine if moderate renal impairment (RI) influenced the pharmacokinetics (PK) and safety of CSL112. Thirty-two subjects, 16 with moderate RI (estimated glomerular filtration rate [eGFR] ≥ 30 and < 60 mL/min/1. Read More

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http://dx.doi.org/10.1002/cpdd.618DOI Listing
September 2018
2 Reads

Effect of a High-Fat Meal on the Pharmacokinetics of the HIV Integrase Inhibitor Cabotegravir.

Clin Pharmacol Drug Dev 2018 Sep 19. Epub 2018 Sep 19.

ViiV Healthcare, Research Triangle Park, NC, USA.

Cabotegravir is an integrase inhibitor in clinical development for the treatment and prevention of HIV infection using oral tablets for short-term, lead-in use before subsequent administration of a long-acting injectable formulation. This phase 1, single-center, randomized, 2 × 2 crossover study evaluated the effect of a high-fat meal on the pharmacokinetics (PK) of oral cabotegravir. Healthy adults received oral cabotegravir 30 mg as a single dose on 2 separate occasions, either after fasting or following a high-fat meal (∼53% fat, ∼870 kcal). Read More

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http://doi.wiley.com/10.1002/cpdd.620
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http://dx.doi.org/10.1002/cpdd.620DOI Listing
September 2018
13 Reads