AtherosclerosisPhase 1NCT01154114
Study to Evaluate Darapladib in Moderately Hepatically Impaired Subjects
A Phase 1 study testing darapladib in people with Atherosclerosis, run by GlaxoSmithKline at 2 sites in United States.
Trial summary
The purpose of this study is to determine any differences in pharmacokinetic parameters of darapladib when dosed to people with moderate liver disease as compared to when dosed in normal healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- darapladib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jul 2010to 15 Oct 2010
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- A male or female is eligible to enter and participate in this study if he/she is a healthy subject OR a moderately hepatically impaired subject with a Child-Pugh score of 7-9.
- Age between 18 and 65 years inclusive, at the time of signing the informed consent.
- Body mass index (BMI) within the range of 19-37kg/m2
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcB < 480 msec in all subjects, including those with bundle branch block at screening ECG
- Healthy subjects only: AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%)
Who cannot join
- Hepatically Impaired Group:
- A positive pre-study drug/alcohol screen, except where subject has prescription for pain or anxiolytic medication that would cause positive test.
- Subjects using any concurrent prohibited medication, and/or receiving concurrent therapy that cannot be safely discontinued and is not approved by the investigator
- 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 four new chemical entities within 12 months prior to the first dosing day.
- Consumption of grapefruit or grapefruit juice > 8oz within 7 days prior to first dose of study medication.
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- Currently receiving oral or injectable strong CYP3A4 inhibitor(s)
- Subjects with any predisposing condition including malabsorption syndromes that might interfere with the absorption, distribution, metabolism, or excretion of drugs (except for hepatic impairment) or any previous gastrointestinal (GI) surgery (except appendectomy or gall bladder removal more than three months prior to the study).
- 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 medical monitor, contraindicates their participation.
- History of anaphylaxis, or anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
- Subjects with fluctuating or rapidly deteriorating hepatic function. Subjects should be medically stable in the opinion of the principal investigator, evidenced by liver function tests as well as clinical signs and symptoms for 30 days before the study.
- Subjects with advanced ascites (Grade 3) or subjects with moderate or severe encephalopathy (Grade 3 or 4) as judged by the investigator.
- History of sensitivity to heparin or heparin-induced thrombocytopenia (if heparin is to be used for flushing a cannula).
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Use of oral, injected and implanted hormonal methods of contraception for female subjects.
- Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
- Lactating females.
- Subjects with a positive HIV antibody test.
- Subjects with creatinine clearance less than or equal to 60 mL/min (calculated by the Cockcroft-Gault Formula)
- Subjects who, within the past two months, have had a history of drug or alcohol abuse or any indication of regular use of more than two units per day
- Subjects with signs of active infection with constitutional symptoms.
- Subjects with esophageal variceal bleeding, unless if banded and stable, within the past 6 months.
- Subjects with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug.
- Subjects with any history of heart failure.
- Subjects with unstable coronary heart disease (unstable angina, acute coronary syndrome, or unstable cardiac rhythm) within the past 6 months.
- Subjects with any other medical condition which, in the judgement of the investigator and medical monitor, could jeopardize safety or welfare of the subject and/or the integrity of the data derived from that subject.
- Severe asthma that is poorly controlled on pharmacotherapy
- Subjects with a risk of non-compliance in following directions or adhering to study restrictions or any subject that the principal investigator deems unsuitable for continuation in study conduct.
- Healthy Volunteer matched group:
- A positive pre-study drug/alcohol screen.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody or positive Hepatitis A IGM antibody result within 3 months of screening
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study
- 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, or 5 half-lives of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- 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, unless in the opinion of the Investigator and medical monitor the medication will not interfere with the study procedures or compromise subject safety.
- Currently receiving oral or injectable strong CYP3A4 inhibitor(s)
- Consumption of grapefruit or grapefruit juice > 8oz within 7 days prior to first dose of study medication.
- Alcohol or drug abuse within the past 6 months, or current mental condition (psychiatric disorder, senility or dementia), which may affect study compliance or prevent understanding of the aims, investigational procedures or possible consequences of the study
- 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 medical monitor, contraindicates their participation.
- History of anaphylaxis, or anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
- Severe asthma that is poorly controlled on pharmacotherapy
- History of cholecystectomy or biliary tract disease, or a history of liver disease with elevated liver function tests of known or unknown etiology.
- History of sensitivity to heparin or heparin-induced thrombocytopenia (if heparin is to be used for flushing a cannula).
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Use of oral, injected and implanted hormonal methods of contraception for female subjects.
- Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
GSK Investigational Site
Miami, Florida, 33143
GSK Investigational Site
Orlando, Florida, 32809
About this study
Official title: An Open-Label, Non-Randomized, Pharmacokinetic and Safety Study of Multiple Oral Doses of SB-480848 in Healthy Subjects and Subjects With Moderate Hepatic Impairment
The purpose of this study is to determine any differences in pharmacokinetic parameters of darapladib when dosed to people with moderate liver disease as compared to when dosed in normal healthy volunteers.
Read the detailed description
This study is an open-label, non-randomised study to assess the pharmacokinetics and safety/tolerability of repeat oral 40 mg doses of darapladib in subjects with moderate hepatic impairment (as defined by a Child-Pugh score of 7-9) in comparison to matched healthy volunteers.
The hepatically impaired and healthy volunteer groups will receive repeat oral doses of darapladib for 10 consecutive days. The pharmacokinetics of darapladib and its metabolites will be evaluated. The effect of liver impairment on the plasma protein binding of darapladib and metabolites will also be determined as data permit. Safety will be assessed by clinical laboratory tests (hematology, chemistry and urinalysis), vital signs (blood pressure and heart rate measurements), 12-lead electrocardiograms (ECGs) and monitoring for adverse events (AEs).
Subjects will be housed in the clinical unit from the evening before first dose until 24 hours after the final dose of 10 days of repeat dosing. A follow-up period will include 2 visits, one of which will be conducted approximately 10-14 days from the last dose of study drug and the second visit will be 35 days +/- one week after the last dose of study drug
- Conditions
- Atherosclerosis
- Being tested
- darapladib
- Keywords
- healthy volunteer, hepatic impairment, darapladib, atherosclerosis
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
darapladibDrug
darapladib 40 mg oral dose
| Study group | Role | What they receive |
|---|---|---|
| moderate hepatic impaired subjects | Experimental | Male and female subjects with moderate hepatic impairment defined by a Child-Pugh score of 7-9 will be included. The subjects will be administered 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets daily for 10 consecutive days. Receives: Drug: darapladib |
| normal healthy volunteers | Experimental | Healthy male and female subjects will be included and will be matched as closely as possible to the group of moderate hepatic impairment subjects for gender, age and body mass index. Each subject will receive daily 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets for 10 consecutive days. Receives: Drug: darapladib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic endpoints will include darapladib AUC (0-τ), Cmax and Tmax. Metabolites pharmacokinetic parameters AUC (0-τ), Cmax and Tmax will be evaluated as data permit.
Measured: After 10 days of repeat dosing
Clinical safety data (spontaneous AE reporting, vital signs, nursing/physician observation, and clinical laboratory tests) will be the primary safety endpoint
Measured: Over 10 days of repeat dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2010 (estimated)
- Study start1 Jul 2010
- Primary completion15 Oct 2010
- Study completion15 Oct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- 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
- NCT01154114
- Sponsor's protocol ID
- 480848/028
- Status last verified
- Jul 2017
- First submitted
- 29 Jun 2010
- Last updated
- 26 Jul 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.
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Non-Randomized, Pharmacokinetic and Safety Study of Multiple Oral Doses of SB-480848 in Healthy Subjects and Subjects With Moderate Hepatic Impairment
- ClinicalTrials.gov ID
- NCT01154114
- Acronym / sponsor ID
- 480848/028
- Conditions
- Atherosclerosis
- Keywords
- healthy volunteer, hepatic impairment, darapladib, atherosclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2010 (actual)
- Primary completion
- 15 Oct 2010 (actual)
- Study completion
- 15 Oct 2010 (actual)
- First posted
- 30 Jun 2010 (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.
The purpose of this study is to determine any differences in pharmacokinetic parameters of darapladib when dosed to people with moderate liver disease as compared to when dosed in normal healthy volunteers.
Detailed description
This study is an open-label, non-randomised study to assess the pharmacokinetics and safety/tolerability of repeat oral 40 mg doses of darapladib in subjects with moderate hepatic impairment (as defined by a Child-Pugh score of 7-9) in comparison to matched healthy volunteers.
The hepatically impaired and healthy volunteer groups will receive repeat oral doses of darapladib for 10 consecutive days. The pharmacokinetics of darapladib and its metabolites will be evaluated. The effect of liver impairment on the plasma protein binding of darapladib and metabolites will also be determined as data permit. Safety will be assessed by clinical laboratory tests (hematology, chemistry and urinalysis), vital signs (blood pressure and heart rate measurements), 12-lead electrocardiograms (ECGs) and monitoring for adverse events (AEs).
Subjects will be housed in the clinical unit from the evening before first dose until 24 hours after the final dose of 10 days of repeat dosing. A follow-up period will include 2 visits, one of which will be conducted approximately 10-14 days from the last dose of study drug and the second visit will be 35 days +/- one week after the last dose of study drug
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| moderate hepatic impaired subjects | Experimental | Drug: darapladibMale and female subjects with moderate hepatic impairment defined by a Child-Pugh score of 7-9 will be included. The subjects will be administered 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets daily for 10 consecutive days. |
| normal healthy volunteers | Experimental | Drug: darapladibHealthy male and female subjects will be included and will be matched as closely as possible to the group of moderate hepatic impairment subjects for gender, age and body mass index. Each subject will receive daily 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets for 10 consecutive days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- A male or female is eligible to enter and participate in this study if he/she is a healthy subject OR a moderately hepatically impaired subject with a Child-Pugh score of 7-9.
- Age between 18 and 65 years inclusive, at the time of signing the informed consent.
- Body mass index (BMI) within the range of 19-37kg/m2
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcB < 480 msec in all subjects, including those with bundle branch block at screening ECG
Key exclusion criteria (50 listed)
- Hepatically Impaired Group:
- A positive pre-study drug/alcohol screen, except where subject has prescription for pain or anxiolytic medication that would cause positive test.
- Subjects using any concurrent prohibited medication, and/or receiving concurrent therapy that cannot be safely discontinued and is not approved by the investigator
- 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 four new chemical entities within 12 months prior to the first dosing day.
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 |
|---|---|---|
| darapladibdarapladib 40 mg oral dose | Drug | moderate hepatic impaired subjects, normal healthy volunteers |
Primary outcome
Pharmacokinetic endpoints will include darapladib AUC (0-τ), Cmax and Tmax. Metabolites pharmacokinetic parameters AUC (0-τ), Cmax and Tmax will be evaluated as data permit.
Time frame: After 10 days of repeat dosing
Clinical safety data (spontaneous AE reporting, vital signs, nursing/physician observation, and clinical laboratory tests) will be the primary safety endpoint
Time frame: Over 10 days of repeat dosing
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 26 Jul 2017.
- Results for study 480848/028 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.
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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
2 sites 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 in people with Atherosclerosis, run by GlaxoSmithKline at 2 sites in United States.
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 6 inclusion and 50 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 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
Pharmacokinetic endpoints will include darapladib AUC (0-τ), Cmax and Tmax. Metabolites pharmacokinetic parameters AUC (0-τ), Cmax and Tmax will be evaluated as data permit. (time frame: After 10 days of repeat dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jul 2017.