Dolutegravir Interactions With Artemisinin-based Combination Therapies

• Status: Completed
• Trial end date: 2016-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Malaria and HIV are found in the same regions of the world and developing countries are most affected by both diseases. For malaria, new drugs have been introduced called ACTs. These drugs are effective against malaria but little is known about how the levels of these drugs in blood relate to how effective these drugs are. For HIV, a new drug has been developed called dolutegravir which has potential to be widely used in developing countries. This proposal will explore how dolutegravir affects the drug levels of these antimalarial drugs and vice versa. In total, 46 healthy volunteers will participate in this study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Liverpool
• Collaborators: Makerere University; ViiV Healthcare
• Treatments: Amodiaquine; Artemether; Artemether-lumefantrine combination; Artemether, Lumefantrine Drug Combination; Artemisinine; Artemisinins; Artesunate; Dolutegravir; Lumefantrine

Criteria

Inclusion Criteria:

1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.

2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

3. Men and women aged 18 years and above

4. Weight ≥40 kg

5. HIV antibody negative at screening.

6. Malaria blood film negative at screening

7. Willing to use mosquito bednets routinely for the duration of the study

8. Women of childbearing potential must be willing to use an effective barrier contraception method for the duration of the study.

Exclusion Criteria:

1. Significant disease affecting cardiac, respiratory, gastrointestinal or neurological symptoms which in the clinician's medical judgment could be worsened by participating in this study or the presence of medical or surgical conditions which could prevent the subject from complying with study procedures.

2. Serum alanine transaminase (ALT) levels above 3x upper limit of normal

3. Serum creatinine levels above 2x upper limit of normal

4. Hepatitis B surface antigen positive

5. Use of medications which are known inducers/inhibitors of CYP or glucuronyl transferase UGT1A1 within past 2 months (e.g. anticonvulsants, TB medications, HIV agents for prophylaxis, azole antifungals)

6. Evidence of QT prolongation on electrocardiogram (ECG) QTc (Rate adjusted QT interval) >450ms (men) or >470ms (women)

7. Pregnant women or female subjects who are unwilling to use a suitable contraceptive method for the duration of the study (condom, diaphragm, IUD or contraceptive implant)

8. Likely to be poorly adherent based on clinician's medical judgement

9. Known to be current injection drug user