Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of 160 mg Enteric-coated Micronised Free Base Darapladib in Healthy Chinese Subjects.
Trial description: This study is to evaluate pharmacokinetics (PK), pharmacodynamics (PD) and safety of 160 mg enteric-coated micronised free base darapladib in healthy Chinese subjects.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Adverse event
Timeframe: Up to 12 weeks
12-lead ECG
Timeframe: Up to 12 weeks
Vital sign measurement
Timeframe: Up to 12 weeks
clinical laboratory examination
Timeframe: Up to 12 weeks
AUC0-t for darapladib
Timeframe: Up to 12 weeks
AUC 0-∞ for Darapdlib
Timeframe: Up to 12 weeks
Cmax for darapladib
Timeframe: Up to 12 weeks
Rcmax for darapladib
Timeframe: Up to 12 weeks
Ro for darapladib
Timeframe: Up to 12 weeks
Nursing/physician observation
Timeframe: Up to 12 weeks
Secondary outcomes:
Tmax for darapladib
Timeframe: Up to 12 weeks
T1/2 for darapladib
Timeframe: Up to 12 weeks
AUC0-t for darapladib metabolite SB-553253 (as data permit).
Timeframe: Up to 12 weeks
AUC0-∞ for darapladib metabolite SB-553253 (as data permit).
Timeframe: Up to 12 weeks
Cmax for darapladib metabolite SB-553253 (as data permit).
Timeframe: Up to 12 weeks
T1/2 for darapladib metabolite SB-553253 (as data permit).
Timeframe: Up to 12 weeks
Tmax for darapladib metabolite SB-553253 (as data permit).
Timeframe: Up to 12 weeks
Plasma Lp-PLA2 activity
Timeframe: Up to 12 weeks
Interventions:
Drug: darapladib 160mg
Enrollment:
24
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Chaoying Hu; Debra Tompson; Mindy Magee; Qian Chen; Yanmei Liu; Wenjing Zhu; Hongxin Zhao; Annette S. Gross; Yun Liu. 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;10(10):e0139862.
Medical condition
Atherosclerosis
Product
darapladib
Collaborators
Not applicable
Study date(s)
October 2013 to January 2014
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 45 years
Accepts healthy volunteers
Yes
- Healthy Chinese males or females aged between 18 and 45 years of age inclusive, at the time of signing the informed consent. (Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A Subject with a clinical abnormality or laboratory parameters which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator (in consultation with the GSK Medical Monitor if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. )
- Of Chinese origin – defined as being born in mainland China, having four ethnic Chinese grandparents.
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- Healthy Chinese males or females aged between 18 and 45 years of age inclusive, at the time of signing the informed consent. (Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A Subject with a clinical abnormality or laboratory parameters which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator (in consultation with the GSK Medical Monitor if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. )
- 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.
Exclusion criteria:
- 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.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication.
- A positive test for Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody result, or positive test for human immunodeficiency virus (HIV) antibody or Syphilis antibody at Screening.
- A positive pre-study drug/alcohol screen.
- Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
- A chest X-ray or computed tomography (CT) scan that reveals evidence of clinical significant abnormalities eg, tuberculosis. A chest X-ray must be taken at Day-1 if a chest X-ray or CT scan is not available within 6 months prior to that day.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Lactating females.
- The Subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2014-04-01
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 117326 can be found on the GSK Clinical Study Register.
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