Darapladib China PK

NCT02000804 | Completed Phase 1

• 1 other identifier: 117326
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate pharmacokinetics (PK), pharmacodynamics (PD) and safety of 160 mg enteric-coated micronised free base darapladib in healthy Chinese subjects.

Conditions

Atherosclerosis

Keywords

Darapladib, Safety, Pharmacokinetics, Pharmacodynamics, Healthy Chinese Subjects

Outcome Measures

Primary Outcomes (10)

• Adverse event

  An AE is any untoward medical occurrence in a patient or clinical investigation Subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  Up to 12 weeks

• 12-lead ECG

  12-lead ECGs will be obtained at designated timepoint during the study, using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.

  Up to 12 weeks

• Vital sign measurement

  Systolic and diastolic blood pressure and pulse rate

  Up to 12 weeks

• clinical laboratory examination

  Hematology, clinical chemistry, urinalysis and additional parameters to be tested

  Up to 12 weeks

• AUC0-t for darapladib

  Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration

  Up to 12 weeks

• AUC 0-∞ for Darapdlib

  Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time

  Up to 12 weeks

• Cmax for darapladib

  Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time

  Up to 12 weeks

• Rcmax for darapladib

  Accumulation ratios Cmax accumulation ratio

  Up to 12 weeks

• Ro for darapladib

  Accumulation ratios Cmax accumulation ratio

  Up to 12 weeks

• Nursing/physician observation

  The physical examination will include assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).

  Up to 12 weeks

Secondary Outcomes (8)

• Tmax for darapladib

  Up to 12 weeks

• T1/2 for darapladib

  Up to 12 weeks

• AUC0-t for darapladib metabolite SB-553253 (as data permit).

  Up to 12 weeks

• AUC0-∞ for darapladib metabolite SB-553253 (as data permit).

  Up to 12 weeks

• Cmax for darapladib metabolite SB-553253 (as data permit).

  Up to 12 weeks

Study Arms (1)

darapladib 160mg

EXPERIMENTAL

drug

Drug: darapladib 160mg

Interventions

darapladib 160mg DRUG

drug

darapladib 160mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Of Chinese origin - defined as being born in mainland China, having four ethnic Chinese grandparents.
• Body weight ≥50 kg and BMI within the range 19 to 24 kg/m2 (inclusive).
• A female Subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy \[for this definition, "documented" refers to the outcome of the investigator's/designee's review of the Subject's medical history for study eligibility, as obtained via a verbal interview with the Subject or from the Subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 MlU/ml and estradiol \< 40 pg/ml (\<147 pmol/L) is confirmatory\].
• Child-bearing potential with negative pregnancy test as determined by urine human chorionic gonadotropin (hCG) test at screening or prior to dosing and Agrees to use 1 of the contraception methods listed in Section 4.3.1 from the time of Screening to sufficiently minimize the risk of pregnancy at that point. Female Subjects must agree to use contraception until the follow-up contact.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• Alanine aminotransferase (ALT), alkaline phosphatise (ALP) and bilirubin ≤1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period:
• QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) \<450 msec; QTc \<480 msec in Subjects with Bundle Branch Block.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• Consumption of grapefruit or grapefruit juice within 7 days prior to first dose of study medication.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History of asthma, anaphylaxis or anaphylactoid reactions, severe allergic responses.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Shanghai, 200030, China

Location

Related Publications (1)

• Hu C, Tompson D, Magee M, Chen Q, Liu YM, Zhu W, Zhao H, Gross AS, Liu Y. Single and Multiple Dose Pharmacokinetics, Pharmacodynamics and Safety of the Novel Lipoprotein-Associated Phospholipase A2 Enzyme Inhibitor Darapladib in Healthy Chinese Subjects: An Open Label Phase-1 Clinical Trial. PLoS One. 2015 Oct 14;10(10):e0139862. doi: 10.1371/journal.pone.0139862. eCollection 2015.

  PMID: 26465780 DERIVED

Related Links

• Results for study 117326 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Atherosclerosis

Interventions

darapladib

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: December 4, 2013
• Study Start: October 23, 2013
• Primary Completion: January 4, 2014
• Study Completion: January 4, 2014
• Last Updated: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)