A Clinical Study Investigating Rifampicin and Dolutegravir in Combination in Healthy Volunteers

NCT03199690 | Unknown Phase 1

• 1 other identifier: SSCR103
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to see how the drug Dolutegravir is broken down by your body, when taken with another drug called Rifampicin. Dolutegravir is given to people as a treatment for HIV. Rifampicin is given to people as a treatment for tuberculosis.

Conditions

HIV-1-infection; Tuberculosis

Outcome Measures

Primary Outcomes (5)

• To investigate the pharmacokinetics of DTG 50 or 100 mg OD in the presence of RIF 600 mg OD in healthy volunteers as measured by trough concentration (Ctrough)

  Ctrough is defined as the concentration at 24 hours after the observed drug dose.

  43 days

• To investigate the pharmacokinetics of DTG 50 or 100 mg OD in the presence of RIF 600 mg OD in healthy volunteers as measured by maximum observed plasma concentration (Cmax)

  Maximum observed plasma concentration (Cmax).

  43 days

• To investigate the pharmacokinetics of DTG 50 or 100 mg OD in the presence of RIF 600 mg OD in healthy volunteers as measured by elimination half-life (t1/2)

  Elimination half-life (t1/2)

  43 days

• To investigate the pharmacokinetics of DTG 50 or 100 mg OD in the presence of RIF 600 mg OD in healthy volunteers as measured by time point at Cmax (Tmax)

  Time point at Cmax (Tmax)

  43 days

• To investigate the pharmacokinetics of DTG 50 or 100 mg OD in the presence of RIF 600 mg OD in healthy volunteers as measured by total drug exposure.

  Total drug exposure, expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h).

  43 days

Study Arms (1)

Single arm

EXPERIMENTAL

Single arm trial design based on the dosing regimen below: Day 1 - 7 \- Dolutegravir 50 mg once daily with food Day 8 - 14 - Dolutegravir 100 mg once daily with food Day 15 - 28 \- Rifampicin 600 mg once daily Day 29 - 35 - Rifampicin 600 mg once daily \& Dolutegravir 50 mg once daily Day 36 - 42 \- Rifampicin 600 mg once daily \& Dolutegravir 100 mg once daily

Drug: Dolutegravir; Drug: Rifampicin

Interventions

Dolutegravir DRUG

Antiviral (integrase inhibitor)

Also known as: Tivicay

Single arm

Rifampicin DRUG

Antibiotic

Also known as: Rifidan

Single arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
• Male or non-pregnant, non-lactating females.
• Between 18 to 60 years, inclusive
• Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive (with weight ≥50kg).
• Alanine aminotransferase, 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.
• Women of childbearing potential (WOCBP - definition in Appendix 4) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 3 months after the study.
• A female may be eligible to enter and participate in the study if she:
• is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
• is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
• True abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications. (When this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception\].
• Any non-hormonal intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion, see protocol appendix 4 for an example listing of approved IUDs);
• Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject; Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of IP.
• True abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications (When this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception\].
• Any non-hormonal intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion, see Appendix 4 for an example listing of approved IUDs);
• Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject; Any contraception method must be used consistently, in accordance with the approved product label and for at least four weeks after discontinuation of IMP.

You may not qualify if:

• Any clinically significant acute or chronic medical illness
• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
• Positive blood screen for hepatitis B surface antigen or C antibody
• Positive blood screen for HIV-1 or 2 by antibody/antigen assay
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Current or recent (within three months) gastrointestinal disease.
• Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
• Exposure to any investigational drug (or placebo) or participation in a clinical study involving the donation of blood samples within three months of first dose of study drug
• Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
• Females of childbearing potential without the use of effective birth control methods, or not willing to continue practising these birth control methods for at least 4 weeks after the end of the treatment period.

Sponsors & Collaborators

• St. Stephens Clinical Research: lead

MeSH Terms

Conditions

Tuberculosis

Interventions

dolutegravir; Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Central Study Contacts

Project manager

CONTACT

0203 828 0593; radio@ststcr.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open label, single centre, sequential pharmacokinetic study

Study Record Dates

• First Submitted: June 20, 2017
• First Posted: June 27, 2017
• Study Start: October 1, 2017
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: October 23, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share