AtherosclerosisPhase 1NCT01873339
Pharmacokinetic Interaction of Darapladib and CYP 3A4 in Healthy Subjects
A Phase 1 study testing Darapladib and Midazolam in people with Atherosclerosis, run by GlaxoSmithKline at 1 site in United States.
Trial summary
This study will determine the effect of single and repeat administration of darapladib, a novel, selective, orally active inhibitor of lipoprotein associated phospholipase A2 (Lp-PLA2) currently under clinical development on the pharmacokinetics of a single oral dose of midazolam, a cytochrome P450 3A4 (CYP3A4) probe… 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 and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jun 2013to 12 Sep 2013
- 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
- Male or female aged between 18 and 65 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 ECG.
- A subject with an alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase or bilirubin laboratory result outside the reference range may be included only if both the Investigator and the GSK Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body mass index within the range 19-37 kilogram per meter square (kg/m2) (inclusive).
- A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with tubal ligation or hysterectomy or postmenopausal defined as 12 months of spontaneous amenorrhea; child-bearing potential and is abstinent or agrees to use the appropriate contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the final follow-up visit; child-bearing potential and has only same-sex partners, when this is her preferred and usual lifestyle.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- Single QTcF (corrected QT calculated using Fridericia's formula)< 450 milliseconds
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 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to any of the study medications, including midazolam and flumazenil, 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.
- Any contraindications for midazolam or flumazenil administration.
- Any condition that, in the opinion of the investigator, presents undue risk from the study medications, including midazolam and flumazenil, or procedures.
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- Requiring the use of oral or injectable strong CYP3A4 inhibitors or use of other CYP3A4 inhibitor/inducers within 14 days prior to dosing.
- History of anaphylaxis, anaphylactoid reactions or severe allergic response.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- Pregnant females as determined by positive hCG test at screening or prior to dosing.
- Where participation in the study would result in donation of blood or blood products in excess of 500mL 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 four new chemical entities within 12 months prior to the first dosing day.
- 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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Unwillingness or inability to follow the procedures outlines in the protocol.
- Subject is mentally or legally incapacitated.
- Consumption of grapefruit or grapefruit juice within 7 days prior to the first dose of study medication.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Single-sequence Study to Evaluate the Potential CYP 3A4 Pharmacokinetic Interaction of Darapladib (SB-480848) in Healthy Subjects
This study will determine the effect of single and repeat administration of darapladib, a novel, selective, orally active inhibitor of lipoprotein associated phospholipase A2 (Lp-PLA2) currently under clinical development on the pharmacokinetics of a single oral dose of midazolam, a cytochrome P450 3A4 (CYP3A4) probe substrate. This study will investigate the inductive and inhibitory effect of darapladib on CYP3A4 metabolic pathway.
- Conditions
- Atherosclerosis
- Being tested
- Darapladib, Midazolam
- Keywords
- Drug interaction, healthy volunteer, SB-480848, Lp-PLA2, darapladib, atherosclerosis, midazolam
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DarapladibDrug
The subjects will receive darapladib 160 mg once daily on Days 3-14. It is provided as Enteric coated, free base (micronized) 160 mg tablet.
MidazolamDrug
The subjects will receive a single oral dose of midazolam 5 mg on Day 1, 3 and14. It is provided as syrup. Each mL of syrup contains midazolam hydrochloride equivalent to 2 mg midazolam
| Study group | Role | What they receive |
|---|---|---|
| Darapladib | Experimental | The subjects will receive a single oral dose of midazolam 5 mg on Day 1. The subjects will receive darapladib 160 mg once daily on Days 3-14. The subjects will also receive a single dose of midazolam 5 mg on Day3 and 14. Receives: Drug: Darapladib; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum concentration (Cmax), and area under the time-concentration curve (AUC[0-inf]) of midazolam at Day 1and 14
The effects of repeat oral dosing of darapladib (160mg enteric coated [EC] tablet once daily [QD]) on the pharmacokinetic parameters - Cmax and AUC(0-infinity[inf]) of a single oral dose of midazolam (5 mg) will be evaluated
Measured: Day 1 and 14
Secondary outcomes (4)
AUC(0-inf), Cmax, time to maximum concentration (tmax) and terminal half-life (t1/2) of midazolam at Days 3 and 14
The effects of single oral dose of darapladib (160mg EC tablet QD) as compared to multiple oral doses of darapladib on the pharmacokinetic parameters - Cmax, AUC(0-inf), tmax and t1/2 of the single oral dose of midazolam (5mg) will be evaluated
Measured: Day 3 and 14
tmax and t1/2 of midazolam at Days 1 and 14
The effects of repeat oral dosing of darapladib (160mg EC tablet QD) on the other pharmacokinetic parameters- tmax and t1/2 of a single oral dose of midazolam (5mg) will be evaluated
Measured: Day 1 and 14
AUC(0-inf), Cmax, tmax and t1/2 of midazolam at Days 1 and 3
The effects of single oral dose of darapladib (160mg EC tablet QD) on the other pharmacokinetic parameters- AUC(0-inf), Cmax, tmax and t1/2 of a single oral dose of midazolam (5mg QD) will be evaluated
Measured: Day 1 and 3
Safety and tolerability of repeated oral doses of darapladib (160mg) in combination with midazolam (5mg) as assessed by frequency and severity of adverse events (AE), 12-Lead ECG, vital signs, oxygen saturation/pulse oximetry and safety laboratory tests
An AE is any untoward medical occurrence temporally associated with the use of the medicinal product, whether or not considered associated with the product. A serious AE is any medical occurrence that results in death, is life-threatening, require hospitalization or prolongation of an existing hospital stay, results in disability or incapacity, congenital anomaly, or is an "Hy's Law event (type of drug-induced liver injury)
Measured: Up to 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2013 (estimated)
- Study start19 Jun 2013
- Primary completion12 Sep 2013
- Study completion12 Sep 2013
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 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
- NCT01873339
- Sponsor's protocol ID
- 115678
- Status last verified
- May 2017
- First submitted
- 6 Jun 2013
- Last updated
- 15 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- 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 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-sequence Study to Evaluate the Potential CYP 3A4 Pharmacokinetic Interaction of Darapladib (SB-480848) in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01873339
- Acronym / sponsor ID
- 115678
- Conditions
- Atherosclerosis
- Keywords
- Drug interaction, healthy volunteer, SB-480848, Lp-PLA2, darapladib, atherosclerosis, midazolam
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 19 Jun 2013 (actual)
- Primary completion
- 12 Sep 2013 (actual)
- Study completion
- 12 Sep 2013 (actual)
- First posted
- 10 Jun 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 will determine the effect of single and repeat administration of darapladib, a novel, selective, orally active inhibitor of lipoprotein associated phospholipase A2 (Lp-PLA2) currently under clinical development on the pharmacokinetics of a single oral dose of midazolam, a cytochrome P450 3A4 (CYP3A4) probe substrate. This study will investigate the inductive and inhibitory effect of darapladib on CYP3A4 metabolic pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Darapladib | Experimental | Drug: Darapladib, Drug: MidazolamThe subjects will receive a single oral dose of midazolam 5 mg on Day 1. The subjects will receive darapladib 160 mg once daily on Days 3-14. The subjects will also receive a single dose of midazolam 5 mg on Day3 and 14. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female aged between 18 and 65 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 ECG.
- A subject with an alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase or bilirubin laboratory result outside the reference range may be included only if both the Investigator and the GSK Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body mass index within the range 19-37 kilogram per meter square (kg/m2) (inclusive).
- A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with tubal ligation or hysterectomy or postmenopausal defined as 12 months of spontaneous amenorrhea; child-bearing potential and is abstinent or agrees to use the appropriate contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the final follow-up visit; child-bearing potential and has only same-sex partners, when this is her preferred and usual lifestyle.
Key exclusion criteria (20 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 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to any of the study medications, including midazolam and flumazenil, 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.
- Any contraindications for midazolam or flumazenil administration.
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 |
|---|---|---|
| DarapladibThe subjects will receive darapladib 160 mg once daily on Days 3-14. It is provided as Enteric coated, free base (micronized) 160 mg tablet. | Drug | Darapladib |
| MidazolamThe subjects will receive a single oral dose of midazolam 5 mg on Day 1, 3 and14. It is provided as syrup. Each mL of syrup contains midazolam hydrochloride equivalent to 2 mg midazolam | Drug | Darapladib |
Primary outcome
Maximum concentration (Cmax), and area under the time-concentration curve (AUC[0-inf]) of midazolam at Day 1and 14
Time frame: Day 1 and 14
The effects of repeat oral dosing of darapladib (160mg enteric coated [EC] tablet once daily [QD]) on the pharmacokinetic parameters - Cmax and AUC(0-infinity[inf]) of a single oral dose of midazolam (5 mg) will be evaluated
4 secondary outcomes
AUC(0-inf), Cmax, time to maximum concentration (tmax) and terminal half-life (t1/2) of midazolam at Days 3 and 14
Time frame: Day 3 and 14
tmax and t1/2 of midazolam at Days 1 and 14
Time frame: Day 1 and 14
AUC(0-inf), Cmax, tmax and t1/2 of midazolam at Days 1 and 3
Time frame: Day 1 and 3
Safety and tolerability of repeated oral doses of darapladib (160mg) in combination with midazolam (5mg) as assessed by frequency and severity of adverse events (AE), 12-Lead ECG, vital signs, oxygen saturation/pulse oximetry and safety laboratory tests
Time frame: Up to 56 days
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.
- Results for study 115678 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
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 and Midazolam in people with Atherosclerosis, run by GlaxoSmithKline at 1 site 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 7 inclusion and 20 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 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?
Maximum concentration (Cmax), and area under the time-concentration curve (AUC[0-inf]) of midazolam at Day 1and 14 (time frame: Day 1 and 14). 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 15 May 2017.