Infections, Human Immunodeficiency Virus and HepatitisPhase 1NCT01467518
Methadone-Dolutegravir (DTG - GSK1349572) Drug Interaction Study.
A Phase 1 study testing Dolutegravir and Methadone in people with Infections, Human Immunodeficiency Virus and Hepatitis, run by ViiV Healthcare at 1 site in Canada.
Trial summary
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of HIV infection. As HIV-infected subjects may also be receiving methadone for opioid dependence, an evaluation of the potential interaction between DTG and methadone is warranted. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Infections, Human Immunodeficiency Virus and Hepatitis
- What is being tested?
- Dolutegravir and Methadone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2011to Feb 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
- 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 outside the reference range for the population being studied may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with positive serology for hepatitis B or C may be entered at the discretion of the investigator, if there is no evidence of active disease or hepatic impairment and it is not a new diagnosis.
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Subject is enrolled in a methadone maintenance program for at least 12 weeks prior to Period 1, Day 1, and is expected to continue in the program though the duration of this study.
- Subject is receiving a methadone QD regimen that has remained unchanged for 14 days prior to Pre-Screening Visit and the dose is ≤200mg daily.
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented (or self reported history) 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 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 >/=45kg for females and BMI within the range 18.0 - 33.0 kg/m2 (inclusive).
- ALT, alkaline phosphatase and bilirubin </=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- The subject has a positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine, and PCP.
- The subject has a positive pre-study alcohol screen.
- A positive test for HIV antibody.
- Current use of alcohol, which in the investigator's opinion, would compromise subject's safety and/or compliance with the trial procedures, including subjects who are likely to experience withdrawal symptoms upon abstinence.
- 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).
- Subjects using any concurrent prohibited medication. (see Section 9.2, for details on prohibited medications). Use of common medications which are permitted during the study are listed in Section 9.1 (permitted medications).
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- 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.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pomelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 10 days prior to the first dose of study medication.
- Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or or excretion of the study drugs. Subjects with a history of cholecystectomy, peptic ulceration, lower or upper GI bleeding, inflammatory bowel disease or pancreatitis should be excluded.
- Subject has inadequate venous access.
- History of Gilbert's disease.
- 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.
- Exclusion criteria for screening ECG as listed in the protocol.
- 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.
- Heavy smokers (e.g., >20 cigarettes/day) who are unable to abstain for at least 8 hours as required by the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-Label, 2-Period Drug Interaction Study to Assess Steady State Plasma Methadone Enantiomer Pharmacokinetics Following Co-Administration of Methadone QD With Dolutegravir (GSK1349572) 50 mg Twice Daily in Opiate-Dependent, HIV Seronegative Adult Subjects.
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of HIV infection. As HIV-infected subjects may also be receiving methadone for opioid dependence, an evaluation of the potential interaction between DTG and methadone is warranted. The primary objective of this study is to determine whether concomitant administration of DTG can affect the pharmacokinetics (PK) of methadone. As a secondary endpoint, the PK of DTG will be compared to historical data. This study will be open-label with subjects receiving DTG and stable doses of methadone. The study will be conducted at one center in Canada in adult male and female subjects.
Read the detailed description
The study is an open label methadone- doltegravir (DTG, GSK1349572) drug interaction study consist of 2 periods. Subjects must be opiate-dependent and are HIV sero-negative and are on stable dose of methadone 14 days prior to pre-screening. After meeting all eligible criterions, subjects will remain on their individual methadone dose for 3 days in period 1. In period 2, subjects will continue on their individual stable dose of methadone and will receive 50 mg DTG every 12 hours for 5 days. Pharmacokinetics will be collected on Day 3 of period 1 and Day 5 of period 2. Safety measurements will be routine chemistry, haematology and urinalysis. Pharmacodynamic parameters for pupillometry and opioid symptom questionnaire will be collected at the same timepoints as for the pharmacokinetics. Subjects will be discharged after the last PK sample has been collected. A follow-up visit will occur 7-14 days after the last dose of study drug. This study will be conducted at one centre in Canada.
- Being tested
- Dolutegravir, Methadone
- Keywords
- methadone, Opiate-dependent
- Medical subject headings
- Infections, Acquired Immunodeficiency Syndrome, Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV. Dose of 50mg every 12 hours for 5 days.
MethadoneDrug
Methadone is a synthetic opioid used in the treatment of opioid dependence. Subjects will be on individualize stabe dose for 8 days.
| Study group | Role | What they receive |
|---|---|---|
| Period 1 | Other | Subjects will be on individualize stable dose of methdaone for 8 days. Receives: Drug: Methadone |
| Period 2 | Other | Subjects will be on individualize stable dose of methadone and open label doses of 50mg Dolutegravir (DTG) every 12 hours for 5 days. Receives: Drug: Dolutegravir; Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of Methadone Pharmacokinetics
Steady state total and R-methadone PK measure: AUC (0-t), Cmax and Ct.
Measured: Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 2, 3, 4. 6, 8, 12, 16, and 24 hours post-dose.
Secondary outcomes (3)
Composite of Methadone and DTG Pharmacokinetics
Dolutegravir PK: AUC (0-t), Cmax, C0, Ct, Cmin, and CL/F; Steady state total and R-methadone: C0, Cmin and CL/F; Steady state plasma S-methadone: AUC (0-t), Cmax, C0, Ct, Cmin, CL/F; Ratio of S/R-methadone AUC (0-t); Ratio of S/R-methadone AUC (0-t); Steady state plasma unbound R-methadone plasma concentrations.
Measured: Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hrs post-dose for methadone; pre-dose, 1, 2, 3, 4, 6, 8, and 12 hrs post-dose for DTG. Unbound R-methadone at 3 and 24 hours on Day 3 (Period 1) and Day 5 (Period 2).
Adverse Events -Number of participants with adverse events
Assessed by change from baseline in vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests.
Measured: Pre-screen visit, Day 1 and Day 5 (Period 2)
Composite of Methadone and DTG Pharmacodynamics
Change from baseline in the subject in the overall opiate agonist score and withdrawal score at post-dose and PK concentrations of methadone alone and in combination; Change in the pupillometry parameters from baseline (minimum pupil diameter [CFBmin], pupillometry area over the effect curve [PAOE] and scores at each time point) and PK concentrations of methadone alone and in combination.
Measured: Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 3, 6, 12, and 24 post-dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2011 (estimated)
- Study startDec 2011
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infections, Human Immunodeficiency Virus and HepatitisStudies 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
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 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
- NCT01467518
- Sponsor's protocol ID
- 115698
- Status last verified
- Mar 2012
- First submitted
- 3 Nov 2011
- Last updated
- 9 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, 2-Period Drug Interaction Study to Assess Steady State Plasma Methadone Enantiomer Pharmacokinetics Following Co-Administration of Methadone QD With Dolutegravir (GSK1349572) 50 mg Twice Daily in Opiate-Dependent, HIV Seronegative Adult Subjects.
- ClinicalTrials.gov ID
- NCT01467518
- Acronym / sponsor ID
- 115698
- Keywords
- methadone, Opiate-dependent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Study start
- Dec 2011
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 8 Nov 2011 (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 HIV infection. As HIV-infected subjects may also be receiving methadone for opioid dependence, an evaluation of the potential interaction between DTG and methadone is warranted. The primary objective of this study is to determine whether concomitant administration of DTG can affect the pharmacokinetics (PK) of methadone. As a secondary endpoint, the PK of DTG will be compared to historical data. This study will be open-label with subjects receiving DTG and stable doses of methadone. The study will be conducted at one center in Canada in adult male and female subjects.
Detailed description
The study is an open label methadone- doltegravir (DTG, GSK1349572) drug interaction study consist of 2 periods. Subjects must be opiate-dependent and are HIV sero-negative and are on stable dose of methadone 14 days prior to pre-screening. After meeting all eligible criterions, subjects will remain on their individual methadone dose for 3 days in period 1. In period 2, subjects will continue on their individual stable dose of methadone and will receive 50 mg DTG every 12 hours for 5 days. Pharmacokinetics will be collected on Day 3 of period 1 and Day 5 of period 2. Safety measurements will be routine chemistry, haematology and urinalysis. Pharmacodynamic parameters for pupillometry and opioid symptom questionnaire will be collected at the same timepoints as for the pharmacokinetics. Subjects will be discharged after the last PK sample has been collected. A follow-up visit will occur 7-14 days after the last dose of study drug. This study will be conducted at one centre in Canada.
Study design
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Period 1 | Other | Drug: MethadoneSubjects will be on individualize stable dose of methdaone for 8 days. |
| Period 2 | Other | Drug: Dolutegravir, Drug: MethadoneSubjects will be on individualize stable dose of methadone and open label doses of 50mg Dolutegravir (DTG) every 12 hours for 5 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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 outside the reference range for the population being studied may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with positive serology for hepatitis B or C may be entered at the discretion of the investigator, if there is no evidence of active disease or hepatic impairment and it is not a new diagnosis.
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Subject is enrolled in a methadone maintenance program for at least 12 weeks prior to Period 1, Day 1, and is expected to continue in the program though the duration of this study.
- Subject is receiving a methadone QD regimen that has remained unchanged for 14 days prior to Pre-Screening Visit and the dose is ≤200mg daily.
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented (or self reported history) 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 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 (22 listed)
- The subject has a positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine, and PCP.
- The subject has a positive pre-study alcohol screen.
- A positive test for HIV antibody.
- Current use of alcohol, which in the investigator's opinion, would compromise subject's safety and/or compliance with the trial procedures, including subjects who are likely to experience withdrawal symptoms upon abstinence.
- 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).
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 |
|---|---|---|
| DolutegravirDolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV. Dose of 50mg every 12 hours for 5 days. | Drug | Period 2 |
| MethadoneMethadone is a synthetic opioid used in the treatment of opioid dependence. Subjects will be on individualize stabe dose for 8 days. | Drug | Period 1, Period 2 |
Primary outcome
Composite of Methadone Pharmacokinetics
Time frame: Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 2, 3, 4. 6, 8, 12, 16, and 24 hours post-dose.
Steady state total and R-methadone PK measure: AUC (0-t), Cmax and Ct.
3 secondary outcomes
Composite of Methadone and DTG Pharmacokinetics
Time frame: Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hrs post-dose for methadone; pre-dose, 1, 2, 3, 4, 6, 8, and 12 hrs post-dose for DTG. Unbound R-methadone at 3 and 24 hours on Day 3 (Period 1) and Day 5 (Period 2).
Adverse Events -Number of participants with adverse events
Time frame: Pre-screen visit, Day 1 and Day 5 (Period 2)
Composite of Methadone and DTG Pharmacodynamics
Time frame: Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 3, 6, 12, and 24 post-dose.
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 9 Apr 2012.
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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 Dolutegravir and Methadone in people with Infections, Human Immunodeficiency Virus and Hepatitis, run by ViiV Healthcare at 1 site in Canada.
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 8 inclusion and 22 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 9 Apr 2012. 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 Canada. 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?
Composite of Methadone Pharmacokinetics (time frame: Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 2, 3, 4. 6, 8, 12, 16, and 24 hours post-dose.). 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 9 Apr 2012.