Infection, Human Immunodeficiency VirusPhase 1NCT01563328
A Study to Evaluate the Effect of Boceprevir and Telaprevir on Dolutegravir Pharmacokinetics in Healthy Adult Subjects (ING115697).
A Phase 1 study testing DTG, BCV and TVR in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 1 site in United States.
Trial summary
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of human immunodeficiency virus (HIV) infection. Co-infection with Hepatitis C (HCV) is common in HIV-infected subjects therefore it is expected that DTG will be coadministered with treatments… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Infection, Human Immunodeficiency Virus
- What is being tested?
- DTG, BCV and TVR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2012to 1 May 2012
- 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
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.
- Single QTcB <or= 450 msec. A single repeat is allowed for eligibility determination.
- 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 a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with haemoglobin, WBC or neutrophil count values outside the normal range should always be excluded from enrollment. A single repeat is allowed for eligibility determination.
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- 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; 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 and is abstinent1 or agrees to use one of the contraception methods listed in Section 8.1 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 follow-up visit.
- Body weight ≥ 50 kg for males and 45 kg for females and BMI within the range 18.5- 31.0 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A positive test for HIV antibody.
- 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.
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- 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).
- 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 islonger) 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.
- 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.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
- Pregnant females as determined by positive serum or urine 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.
- If heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
- Unable to refrain from consumption of seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices containing these products from 7 days prior to the first dose of study medication.
- The subject's systolic blood pressure at screening visit is outside the range of 90- 140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects. A single repeat is allowed for eligibility determination.
- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Males Females Heart rate <45 and >100 bpm <50 and >100 bpm PR Interval <120 and >220 msec QRS duration <70 and >120 msec QTc interval (Bazett) >450 msec
- Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization).
- Any clinically significant arrhythmia, any clinically significant conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses>3 seconds, and non-sustained or sustained ventricular tachycardia (≥3 consecutive ventricular ectopic beats).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open Label, Randomized, Two Cohort, Two Period, Oneway Study to Evaluate the Effect of Boceprevir and Telaprevir onDolutegravir Pharmacokinetics in Healthy Adult Subjects (ING115697)
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of human immunodeficiency virus (HIV) infection. Co-infection with Hepatitis C (HCV) is common in HIV-infected subjects therefore it is expected that DTG will be coadministered with treatments for HCV. Boceprevir (BCV) and Telaprevir (TVR) are protease inhibitors for the treatment of HCV that were recently approved by the Food and Drug Administration/European Medicines Agency (FDA/EMA) and have rapidly been adopted to "standard of care" in combination with pegylated interferon and ribavarin. This is a single-center, open-label, two-cohort, two-period, one-way, study in healthy adult subjects. A total of approximately 32 subjects will be enrolled, in order to obtain 24 evaluable subjects (12 per cohort). In the first treatment period, all subjects will receive DTG 50 mg once daily for 5 days (treatment A). In period 2, subjects will receive DTG 50 mg once daily plus either BCV 800 mg q8h (treatment B) for 10 days or TVR 750 mg q8h (treatment C) for 10 days. There will be no washout between treatments. Safety evaluations and serial PK samples will be collected during each treatment period.
Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug.
This study will be conducted at one center in the US, with healthy adult male and female subjects.
- Conditions
- Infection, Human Immunodeficiency Virus
- Being tested
- DTG, BCV, TVR
- Keywords
- Dolutegravir, GSK1349572, DTG, BCV, TVR, drug interaction
- Medical subject headings
- Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTGDrug
Also called Dolutegravir
50 mg q24h
BCVDrug
Also called Boceprevir
800 mg q8h
TVRDrug
Also called Telaprevir
750 mg q8h
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | DTG x 5 days followed by BCV + DTG x 10 days Receives: Drug: DTG; Drug: BCV |
| Cohort 2 | Experimental | DTG x 5 days followed by TVR + DTG x 10 days Receives: Drug: DTG; Drug: TVR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma steady-state DTG PK parameters AUC(0-τ), Cmax, Cmin, and Cτ
Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose
Measured: For 24 hours after dosing on Period 1 Day 5 and Period 2 Day 10
Secondary outcomes (4)
Safety and tolerability parameters as assessed by change from baseline in vital signs n(BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests.
Measured: Up to 29 days
Plasma steady-state DTG tmax and t1/2
Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose
Measured: For 24 hours after dosing on Period 1 Day 5 and Period 2 Day 10
Plasma steady-state TVR and BCV AUC(0-t), Cmax, Cmin, and Ct
Samples will be collected at predose and at 1, 2, 3, 4, and 8 hours post dose
Measured: For 8 hours after dosing on Period 2, Day 10
Plasma steady-state TVR and BCV tmax and t1/2
Samples will be collected at predose and at 1, 2, 3, 4, and 8 hours post dose
Measured: For 8 hours after dosing on Period 2, Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2012 (estimated)
- Study start1 Mar 2012
- Primary completion1 May 2012
- Study completion1 May 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Infection, Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01563328
- Sponsor's protocol ID
- 115697
- Status last verified
- Mar 2017
- First submitted
- 22 Mar 2012
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Johnson M, Borland J, Chen S, et al. The effect of boceprevir and telaprevir on dolutegravir pharmacokinetics in healthy adult subjects. Published at: International Workshop on Clinical Pharmacology of HIV Therapy - 14th Annual; April 22-24, 2013; Amsterdam, the Netherlands.
Johnson M, Borland J, Chen S, Savina P, Wynne B, Piscitelli S. Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir. Br J Clin Pharmacol. 2014 Nov;78(5):1043-9. doi: 10.1111/bcp.12428.
PubMed 24838177
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open Label, Randomized, Two Cohort, Two Period, Oneway Study to Evaluate the Effect of Boceprevir and Telaprevir onDolutegravir Pharmacokinetics in Healthy Adult Subjects (ING115697)
- ClinicalTrials.gov ID
- NCT01563328
- Acronym / sponsor ID
- 115697
- Conditions
- Infection, Human Immunodeficiency Virus
- Keywords
- Dolutegravir, GSK1349572, DTG, BCV, TVR, drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Study start
- 1 Mar 2012
- Primary completion
- 1 May 2012 (actual)
- Study completion
- 1 May 2012 (actual)
- First posted
- 26 Mar 2012 (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.
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of human immunodeficiency virus (HIV) infection. Co-infection with Hepatitis C (HCV) is common in HIV-infected subjects therefore it is expected that DTG will be coadministered with treatments for HCV. Boceprevir (BCV) and Telaprevir (TVR) are protease inhibitors for the treatment of HCV that were recently approved by the Food and Drug Administration/European Medicines Agency (FDA/EMA) and have rapidly been adopted to "standard of care" in combination with pegylated interferon and ribavarin. This is a single-center, open-label, two-cohort, two-period, one-way, study in healthy adult subjects. A total of approximately 32 subjects will be enrolled, in order to obtain 24 evaluable subjects (12 per cohort). In the first treatment period, all subjects will receive DTG 50 mg once daily for 5 days (treatment A). In period 2, subjects will receive DTG 50 mg once daily plus either BCV 800 mg q8h (treatment B) for 10 days or TVR 750 mg q8h (treatment C) for 10 days. There will be no washout between treatments. Safety evaluations and serial PK samples will be collected during each treatment period.
Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug.
This study will be conducted at one center in the US, with healthy adult male and female subjects.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: DTG, Drug: BCVDTG x 5 days followed by BCV + DTG x 10 days |
| Cohort 2 | Experimental | Drug: DTG, Drug: TVRDTG x 5 days followed by TVR + DTG x 10 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.
- Single QTcB <or= 450 msec. A single repeat is allowed for eligibility determination.
- 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 a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with haemoglobin, WBC or neutrophil count values outside the normal range should always be excluded from enrollment. A single repeat is allowed for eligibility determination.
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- 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; 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 and is abstinent1 or agrees to use one of the contraception methods listed in Section 8.1 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 follow-up visit.
Key exclusion criteria (20 listed)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as:
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 |
|---|---|---|
| DTGAlso: Dolutegravir50 mg q24h | Drug | Cohort 1, Cohort 2 |
| BCVAlso: Boceprevir800 mg q8h | Drug | Cohort 1 |
| TVRAlso: Telaprevir750 mg q8h | Drug | Cohort 2 |
Primary outcome
Plasma steady-state DTG PK parameters AUC(0-τ), Cmax, Cmin, and Cτ
Time frame: For 24 hours after dosing on Period 1 Day 5 and Period 2 Day 10
Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose
4 secondary outcomes
Safety and tolerability parameters as assessed by change from baseline in vital signs n(BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests.
Time frame: Up to 29 days
Plasma steady-state DTG tmax and t1/2
Time frame: For 24 hours after dosing on Period 1 Day 5 and Period 2 Day 10
Plasma steady-state TVR and BCV AUC(0-t), Cmax, Cmin, and Ct
Time frame: For 8 hours after dosing on Period 2, Day 10
Plasma steady-state TVR and BCV tmax and t1/2
Time frame: For 8 hours after dosing on Period 2, Day 10
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 28 Mar 2017.
- BackgroundJohnson M, Borland J, Chen S, et al. The effect of boceprevir and telaprevir on dolutegravir pharmacokinetics in healthy adult subjects. Published at: International Workshop on Clinical Pharmacology of HIV Therapy - 14th Annual; April 22-24, 2013; Amsterdam, the Netherlands.
- Derived from this study: PubMed 24838177Johnson M, Borland J, Chen S, Savina P, Wynne B, Piscitelli S. Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir. Br J Clin Pharmacol. 2014 Nov;78(5):1043-9. doi: 10.1111/bcp.12428.
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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
ViiV Healthcare
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 DTG, BCV and TVR in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare 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 28 Mar 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?
Plasma steady-state DTG PK parameters AUC(0-τ), Cmax, Cmin, and Cτ (time frame: For 24 hours after dosing on Period 1 Day 5 and Period 2 Day 10). 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 NCT01563328, which also lists 2 linked publications.
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 28 Mar 2017.