Read by QxMD icon Read

Clinical Pharmacology in Drug Development

Rajesh Patel, Jonathan L Palmer, Shashidhar Joshi, Alejandro Di Ció Gimena, Florencia Esquivel
Two bioavailability/bioequivalence studies were carried out to evaluate the pharmacokinetics of candesartan cilexetil 16mg tablet formulations. A pilot study was used to optimise the formulation and manufacturing process prior to conducting the definitive study. The pilot study was a single dose, randomised two period crossover and the definitive study was a single dose randomised three period, 6 sequence cross over study in healthy adults. In the pilot study the test formulation was 24% and 18% greater for Cmax and AUC compared to the innovator product...
October 18, 2016: Clinical Pharmacology in Drug Development
Michael Burdick, Richard Mamelok, Michele Hurliman, Mariève Dupuis, Yuli Xie, Julie Grenier, Curtis Sheldon, Michael Gartner, Peter Noymer
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits analgesic activity with no sedative or anxiolytic properties. Twelve (12) healthy male subjects were enrolled in a study to receive either one of two treatments over two periods in an open-label, randomized, two-way crossover design: (A) 120 mg of ketorolac tromethamine administered as a continuous subcutaneous (SC) infusion over a 24-hour period; or (B) an identical total daily dose administered as 4 intramuscular (IM) bolus injections of 30 mg each given every 6 hours (current labeled treatment regimen)...
October 14, 2016: Clinical Pharmacology in Drug Development
Seol Ju Moon, Sun-Young Kim, Cheol-Hee Lim, Hwan Bong Jang, Min-Gul Kim, Ji-Young Jeon
We investigated botanical drug-pharmaceutical drug interactions between DW1029 (a botanical extract of Morus alba linne root bark and Puerariae radix) and metformin, losartan, and linagliptin in the steady state. Three studies were conducted as a randomized, open-label, two-period, two-treatment, multiple-dose, two-way crossover designs. Eligible subjects received metformin (500 mg twice daily), losartan (50 mg once daily), or linagliptin (5 mg once daily) with DW1029M (300 mg × 2T twice daily) every 12 h on days 1 through 6 and a single dose in the morning of day 7...
October 14, 2016: Clinical Pharmacology in Drug Development
Thomas Schluep, Jason Lickliter, James Hamilton, David L Lewis, Ching-Lung Lai, Johnson Yn Lau, Stephen A Locarnini, Robert G Gish, Bruce D Given
ARC-520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA-derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase I, randomized, double-blind, placebo-controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01-4.0 mg/kg ARC-520 Injection (N = 36) or placebo (N = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement)...
October 14, 2016: Clinical Pharmacology in Drug Development
Susanne Johansson, Maria Leonsson-Zachrisson, Mikael Knutsson, Andrew G Spencer, Eric D Labonté, Desiree Deshpande, Jill Kohler, Kenji Kozuka, Dominique Charmot, David P Rosenbaum
Tenapanor (RDX5791, AZD1722), a first-in-class small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3. Tenapanor acts locally in the gut where it reduces absorption of sodium and phosphate. It is being studied in patients with chronic kidney disease requiring dialysis, who are often administered phosphate binders such as sevelamer to help control hyperphosphatemia. We investigated whether co-administration of tenapanor with phosphate binders (sevelamer or calcium-based binders) impacts on the pharmacodynamic effects of tenapanor...
September 22, 2016: Clinical Pharmacology in Drug Development
Ulrike Gottwald-Hostalek, Ningling Sun, Christian Barho, Steven Hildemann
Hypertension is currently one of the greatest global healthcare challenges. Although many effective drugs are available, combinations of 2 or more medications are often required to meet clinical targets. Combination therapy has several advantages over monotherapy: lower doses of each drug can be used to achieve therapeutic goals; lower doses may lead to fewer adverse events, facilitating patient adherence; and using multiple drugs with different modes of action may be more effective in treating multifactorial diseases, including hypertension...
September 22, 2016: Clinical Pharmacology in Drug Development
Kazuo Umemura, Yasuhiko Ikeda, Nobuko Matsushima, Kazunao Kondo
We evaluated the pharmacokinetics and pharmacodynamics of prasugrel used in combination with aspirin in healthy Japanese subjects. All subjects received aspirin 100 mg/day. Subsequently, in the single-administration study, 23 subjects also received prasugrel 20 mg or 30 mg; and in the multiple-administration study, 20 subjects received a loading dose of prasugrel 20 mg or 30 mg on day 1, followed by a maintenance dose of prasugrel 5 mg/day or 7.5 mg/day, respectively, on days 2-5. In both studies, the plasma concentration of the active metabolite of prasugrel, R-138727, reached a maximum at 0...
September 22, 2016: Clinical Pharmacology in Drug Development
Peter N Morcos, Neil Parrott, Ludger Banken, Carsten Timpe, Marc Lindenberg, Elena Guerini, Georgina Dall, Katrijn Bogman, Carolina Sturm, Ali Zeaiter, Meret Martin-Facklam, Alex Phipps
The anaplastic lymphoma kinase (ALK) inhibitor alectinib is an effective treatment for ALK-positive non-small-cell lung cancer. This bioequivalence study evaluated the in vivo performance of test 3 formulations with the reduced wetting agent sodium lauryl sulfate (SLS) content. This randomized, 4-period, 4-sequence, crossover study compared alectinib (600 mg) as 25%, 12.5%, and 3% SLS hard capsule formulations with the reference 50% SLS clinical formulation in healthy subjects under fasted conditions (n = 49), and following a high-fat meal (n = 48)...
August 22, 2016: Clinical Pharmacology in Drug Development
Peter N Morcos, Yumi Cleary, Elena Guerini, Georgina Dall, Katrijn Bogman, Luigi De Petris, Santiago Viteri, Walter Bordogna, Li Yu, Meret Martin-Facklam, Alex Phipps
The efficacy and safety of alectinib, a central nervous system-active and selective anaplastic lymphoma kinase (ALK) inhibitor, has been demonstrated in patients with ALK-positive (ALK+) non-small-cell lung cancer (NSCLC) progressing on crizotinib. Alectinib is mainly metabolized by cytochrome P450 3A (CYP3A) to a major similarly active metabolite, M4. Alectinib and M4 show evidence of weak time-dependent inhibition and small induction of CYP3A in vitro. We present results from three fixed-sequence studies evaluating drug-drug interactions for alectinib through CYP3A...
August 22, 2016: Clinical Pharmacology in Drug Development
Steven Christensen, Ed Paluch, Shyamalie Jayawardena, Stephen Daniels, Suzanne Meeves
Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600 mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1) (Study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1) (Study 2). In Study 1 (N = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0...
August 22, 2016: Clinical Pharmacology in Drug Development
Peter N Morcos, Elena Guerini, Neil Parrott, Georgina Dall, Steven Blotner, Katrijn Bogman, Carolina Sturm, Bogdana Balas, Meret Martin-Facklam, Alex Phipps
Alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, is approved for treatment of patients with ALK+ non-small-cell lung cancer who have progressed on, or are intolerant to, crizotinib. This study assessed the effect of a high-fat meal and the proton pump inhibitor, esomeprazole, on the pharmacokinetics (PK) of alectinib. This was an open-label, 2-group study in healthy subjects. In Group 1 (n = 18), subjects were randomly assigned to a 2-treatment (A: fasted conditions, B: following a high-fat meal), 2-sequence (AB or BA) crossover assessment, separated by a 10-day washout...
August 22, 2016: Clinical Pharmacology in Drug Development
Meng Zhang, Laurent Perrin, Patricia Pardo
LIGHT, a member of the TNF superfamily, is potentially involved in mucosal inflammation associated with inflammatory bowel disease. The safety and pharmacokinetics of the fully human monoclonal anti-LIGHT antibody, SAR252067 was evaluated in healthy volunteers in a phase 1 study, as a potential treatment for diseases related to LIGHT-mediated mucosal inflammation. This double-blind, randomized, placebo-controlled, sequential ascending single-dose, single-center, 16-week study randomized 48 subjects to a single subcutaneous dose of SAR252067 (40, 120, 300, 600, 900, or 1200 mg) or placebo...
August 22, 2016: Clinical Pharmacology in Drug Development
Orit Cohen-Barak, Hadas Barkay, Michele Rasamoelisolo, Kathleen Butler, Kazumasa Yamada, Merav Bassan, Esther Yoon, Ofer Spiegelstein
TV-1106 is a human serum albumin genetically fused to recombinant human growth hormone, designed to provide a long-acting alternative to daily GH injections in patients with GH deficiency. This study investigated the pharmacokinetics, pharmacodynamics and safety of single subcutaneous doses of TV-1106 (7.5, 15, 50 and 100mg) in Japanese (n = 44) and Caucasian (n = 44) healthy subjects. TV-1106 pharmacokinetics and pharmacodynamics were comparable in Japanese and Caucasian populations. TV-1106 demonstrated relatively slow absorption (median tmax 10-30 hours) and mean elimination half-life of 26-36 hours...
August 4, 2016: Clinical Pharmacology in Drug Development
(no author information available yet)
No abstract text is available yet for this article.
September 2016: Clinical Pharmacology in Drug Development
Daniel A Tatosian, Nadia Cardillo Marricco, Xiaoli Shirley Glasgow, Bruce DeGroot, Katherine Dunnington, Laura George, Isaias Noel Gendrano, Amy O Johnson-Levonas, Dennis Swearingen, Eunkyung Kauh
Omarigliptin is a dipeptidyl peptidase-4 inhibitor being developed as a once-weekly treatment for type 2 diabetes. This double-blind, double-dummy, randomized, 3-period balanced crossover study definitively evaluated the effects of a supratherapeutic omarigliptin dose on QTc interval. Population-specific correction of QT interval (QTcP) was used for the primary analysis. Healthy subjects (n = 60) were enrolled and received treatments separated by a ≥4-week washout: (1) single-dose 25 mg omarigliptin (day 1), single-dose 175 mg omarigliptin (day 2); (2) placebo (day 1) followed by single-dose 400 mg moxifloxacin (day 2); (3) placebo (days 1 and 2)...
September 2016: Clinical Pharmacology in Drug Development
Carol Addy, Daniel A Tatosian, Xiaoli S Glasgow, Isaias Noel Gendrano Iii, Christine McCrary Sisk, Eunkyung A Kauh, S Aubrey Stoch, John A Wagner
Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women, young obese (30 ≤ body mass index [BMI] ≤ 35 kg/m(2) ) men and women, and young nonobese women of nonchildbearing potential...
September 2016: Clinical Pharmacology in Drug Development
Susanne Johansson, Boel Löfberg, Maria Aunes, Helen Lunde, Lars Frison, Nils Edvardsson, Marie Cullberg
The objectives were to estimate and compare, in silico and in vivo, the effects of a strong and a moderate CYP3A4 inhibitor on AZD1305 pharmacokinetics. In silico, simulations were performed with the computer software Simcyp, and the predicted outcome was compared with the results observed in healthy male subjects. In silico, the geometric mean plasma exposure of AZD1305 + ketoconazole showed a 7.1-fold higher AUC and a 4.4-fold higher Cmax compared with AZD1305 alone. Coadministration with verapamil gave a 1...
September 2016: Clinical Pharmacology in Drug Development
Caroline Dudkowski, Aziz Karim, Melvin Munsaka
Azilsartan medoxomil is a long-acting angiotensin II receptor blocker used to treat hypertension as monotherapy or in fixed-dose combination (FDC) with chlorthalidone. This study assessed the effects of food intake on the plasma pharmacokinetics of the active moiety, azilsartan, and of chlorthalidone when administered as separate tablets or in FDC. Cohort 1 (n = 24) received azilsartan medoxomil (80 mg) and chlorthalidone (25 mg) once in a fasted condition and once 30 minutes after the initiation of a high-fat meal (fed)...
September 2016: Clinical Pharmacology in Drug Development
Isaac Ng, H Karl Greenblatt, David J Greenblatt
No abstract text is available yet for this article.
September 2016: Clinical Pharmacology in Drug Development
Tong Zhu, James Keirns, Corrie Howieson, Atsunori Kaibara, Ronald Goldwater, Alan J Kivitz, Vishala Chindalore, Stanley Cohen, Vicki Santos, Bolanle Akinlade, Robert Kernstock, Leticia Delgado-Herrera, Paul C Blahunka, Erik E Karrer, Jay P Garg, Nancy Samberg, Bernhardt G Zeiher
ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.0 mg/kg or subcutaneously at 0.3 to 3.0 mg/kg. It showed decreased clearance and prolonged half-life with increasing doses, consistent with target-mediated disposition. The apparent bioavailability was 36.3%-56.7% across single subcutaneous doses...
September 2016: Clinical Pharmacology in Drug Development
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"