AtherosclerosisPhase 1NCT02000804
Darapladib China PK
A Phase 1 study testing darapladib 160mg in people with Atherosclerosis, run by GlaxoSmithKline at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- darapladib 160mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 23 Oct 2013to 4 Jan 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of 160 mg Enteric-coated Micronised Free Base Darapladib in Healthy Chinese Subjects.
This study is to evaluate pharmacokinetics (PK), pharmacodynamics (PD) and safety of 160 mg enteric-coated micronised free base darapladib in healthy Chinese subjects.
Read the detailed description
SB-480848 (darapladib) is a novel selective and orally active inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) being developed by GlaxoSmithKline (GSK) for the treatment of atherosclerosis.
This will be an open label study where each Subject will participate in 2 study sessions, a single dose session and a repeat dose session. All Subjects will receive 160 mg of enteric coated micronised free-base darapladib as a single dose and as repeated daily doses for 28 days.
The purpose of this study is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) and safety of single and repeat oral dose of darapladib in healthy Chinese Subjects. The primary endpoints for safety are: clinical safety data from spontaneous adverse event reporting, 12-lead electrocardiogram recording, vital sign measurement, nursing/physician observation and clinical laboratory tests. The primary PK parameters of interest are area under plasma concentration time curve (AUC) and maximum plasma concentration (Cmax) of darapladib, while the secondary PK parameters of interest are: time of occurrence of Cmax (Tmax) and apparent terminal phase half-life (t1/2) of darapladib as well as AUC, Cmax, Tmax and t1/2 of the metabolite, SB-553253. Finally, the PD endpoint of interest is plasma Lp PLA2 activity, as expressed in terms of percent inhibition relative to baseline.
- Conditions
- Atherosclerosis
- Being tested
- darapladib 160mg
- Keywords
- Darapladib, Safety, Pharmacokinetics, Pharmacodynamics, Healthy Chinese Subjects
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
darapladib 160mgDrug
drug
| Study group | Role | What they receive |
|---|---|---|
| darapladib 160mg | Experimental | drug Receives: Drug: darapladib 160mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 12 weeks
Vital sign measurement
Systolic and diastolic blood pressure and pulse rate
Measured: Up to 12 weeks
clinical laboratory examination
Hematology, clinical chemistry, urinalysis and additional parameters to be tested
Measured: 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
Measured: Up to 12 weeks
AUC 0-∞ for Darapdlib
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time
Measured: Up to 12 weeks
Cmax for darapladib
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time
Measured: Up to 12 weeks
Rcmax for darapladib
Accumulation ratios Cmax accumulation ratio
Measured: Up to 12 weeks
Ro for darapladib
Accumulation ratios Cmax accumulation ratio
Measured: Up to 12 weeks
Nursing/physician observation
The physical examination will include assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Measured: Up to 12 weeks
Secondary outcomes (8)
Tmax for darapladib
Time of occurrence of Cmax for darapladib
Measured: Up to 12 weeks
T1/2 for darapladib
Terminal phase half-life for darapladib
Measured: Up to 12 weeks
AUC0-t for darapladib metabolite SB-553253 (as data permit).
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration for the pharmacologically active metabolite SB-553253
Measured: Up to 12 weeks
AUC0-∞ for darapladib metabolite SB-553253 (as data permit).
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time the pharmacologically active metabolite SB-553253
Measured: Up to 12 weeks
Cmax for darapladib metabolite SB-553253 (as data permit).
Maximum observed concentration for the pharmacologically active metabolite SB-553253
Measured: Up to 12 weeks
T1/2 for darapladib metabolite SB-553253 (as data permit).
Terminal phase half-life for the pharmacologically active metabolite SB-553253
Measured: Up to 12 weeks
Tmax for darapladib metabolite SB-553253 (as data permit).
Time of occurrence of Cmax for the pharmacologically active metabolite SB-553253
Measured: Up to 12 weeks
Plasma Lp-PLA2 activity
Percent inhibition relative to baseline of Plasma Lp-PLA2
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2013 (estimated)
- Study start23 Oct 2013
- Primary completion4 Jan 2014
- Study completion4 Jan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02000804
- Sponsor's protocol ID
- 117326
- Status last verified
- May 2017
- First submitted
- 20 Jun 2013
- Last updated
- 15 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
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.
PubMed 26465780
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of 160 mg Enteric-coated Micronised Free Base Darapladib in Healthy Chinese Subjects.
- ClinicalTrials.gov ID
- NCT02000804
- Acronym / sponsor ID
- 117326
- Conditions
- Atherosclerosis
- Keywords
- Darapladib, Safety, Pharmacokinetics, Pharmacodynamics, Healthy Chinese Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 23 Oct 2013 (actual)
- Primary completion
- 4 Jan 2014 (actual)
- Study completion
- 4 Jan 2014 (actual)
- First posted
- 4 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to evaluate pharmacokinetics (PK), pharmacodynamics (PD) and safety of 160 mg enteric-coated micronised free base darapladib in healthy Chinese subjects.
Detailed description
SB-480848 (darapladib) is a novel selective and orally active inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) being developed by GlaxoSmithKline (GSK) for the treatment of atherosclerosis.
This will be an open label study where each Subject will participate in 2 study sessions, a single dose session and a repeat dose session. All Subjects will receive 160 mg of enteric coated micronised free-base darapladib as a single dose and as repeated daily doses for 28 days.
The purpose of this study is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) and safety of single and repeat oral dose of darapladib in healthy Chinese Subjects. The primary endpoints for safety are: clinical safety data from spontaneous adverse event reporting, 12-lead electrocardiogram recording, vital sign measurement, nursing/physician observation and clinical laboratory tests. The primary PK parameters of interest are area under plasma concentration time curve (AUC) and maximum plasma concentration (Cmax) of darapladib, while the secondary PK parameters of interest are: time of occurrence of Cmax (Tmax) and apparent terminal phase half-life (t1/2) of darapladib as well as AUC, Cmax, Tmax and t1/2 of the metabolite, SB-553253. Finally, the PD endpoint of interest is plasma Lp PLA2 activity, as expressed in terms of percent inhibition relative to baseline.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| darapladib 160mg | Experimental | Drug: darapladib 160mgdrug |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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].
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| darapladib 160mgdrug | Drug | darapladib 160mg |
Primary outcome
Adverse event
Time frame: Up to 12 weeks
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.
12-lead ECG
Time frame: Up to 12 weeks
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.
Vital sign measurement
Time frame: Up to 12 weeks
Systolic and diastolic blood pressure and pulse rate
clinical laboratory examination
Time frame: Up to 12 weeks
Hematology, clinical chemistry, urinalysis and additional parameters to be tested
AUC0-t for darapladib
Time frame: Up to 12 weeks
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration
AUC 0-∞ for Darapdlib
Time frame: Up to 12 weeks
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time
Cmax for darapladib
Time frame: Up to 12 weeks
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time
Rcmax for darapladib
Time frame: Up to 12 weeks
Accumulation ratios Cmax accumulation ratio
Ro for darapladib
Time frame: Up to 12 weeks
Accumulation ratios Cmax accumulation ratio
Nursing/physician observation
Time frame: Up to 12 weeks
The physical examination will include assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
8 secondary outcomes
Tmax for darapladib
Time frame: Up to 12 weeks
T1/2 for darapladib
Time frame: Up to 12 weeks
AUC0-t for darapladib metabolite SB-553253 (as data permit).
Time frame: Up to 12 weeks
AUC0-∞ for darapladib metabolite SB-553253 (as data permit).
Time frame: Up to 12 weeks
Cmax for darapladib metabolite SB-553253 (as data permit).
Time frame: Up to 12 weeks
T1/2 for darapladib metabolite SB-553253 (as data permit).
Time frame: Up to 12 weeks
Tmax for darapladib metabolite SB-553253 (as data permit).
Time frame: Up to 12 weeks
Plasma Lp-PLA2 activity
Time frame: Up to 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
- Derived from this study: PubMed 26465780Hu 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.
- Results for study 117326 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Related trials for Atherosclerosis
RecruitingPhase 2
A Study to Evaluate the Efficacy, Safety, Pharmacodynamics (PD), and Pharmacokinetics (PK) of Selnoflast in Reducing Vascular Inflammation in Participants With Atherosclerosis at Risk for Major Adverse Cardiac Events
Atherosclerosis
Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
RecruitingPhase 2
A Study of Clazakizumab (LY5724886) in Adults With Elevated hsCRP and at Increased Risk for Cardiovascular Event
Atherosclerosis, Cardiovascular Disease
Recruiting
Pemafibrate for Symptomatic ICAS RCT
Intracranial Atherosclerotic Disease (ICAD), Hypertriglyceridaemia
Recruiting
Effect of Anifrolumab on Arterial Inflammation in Systemic Lupus Erythematosus Study
Systemic Lupus Erythematosus, Atherosclerosis Generalized
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing darapladib 160mg in people with Atherosclerosis, run by GlaxoSmithKline at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse event (time frame: Up to 12 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02000804, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.