Methadone-Dolutegravir (DTG - GSK1349572) Drug Interaction Study.

NCT01467518 | Completed Phase 1

• 1 other identifier: 115698
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Infections, Human Immunodeficiency Virus and Hepatitis

Keywords

methadone; Opiate-dependent

Outcome Measures

Primary Outcomes (1)

• Composite of Methadone Pharmacokinetics

  Steady state total and R-methadone PK measure: AUC (0-t), Cmax and Ct.

  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

  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

  Pre-screen visit, Day 1 and Day 5 (Period 2)

• Composite of Methadone and DTG Pharmacodynamics

  Day 3 (Period 1) and Day 5 (Period 2) at pre-dose, 1, 3, 6, 12, and 24 post-dose.

Study Arms (2)

Period 1

OTHER

Subjects will be on individualize stable dose of methdaone for 8 days.

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.

Drug: Dolutegravir; Drug: Methadone

Interventions

Dolutegravir DRUG

Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV. Dose of 50mg every 12 hours for 5 days.

Period 2

Methadone DRUG

Methadone is a synthetic opioid used in the treatment of opioid dependence. Subjects will be on individualize stabe dose for 8 days.

Period 1; Period 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead
• Shionogi: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Toronto, Ontario, M5V 2T3, Canada

Location

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; Hepatitis

Interventions

dolutegravir; Methadone

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2011
• First Posted: November 8, 2011
• Study Start: December 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 9, 2012

Record last verified: 2012-03

Locations

CA (1)