Pharmacokinetic Interactions Between Antiretroviral Agents and Antimalarial Drug Combinations

NCT00697892 | Completed Phase 1

• 1 other identifier: H6930-27654
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine in healthy volunteers whether certain anti-HIV medications (lopinavir/ritonavir and efavirenz) affect the drug levels of certain anti-malarial medications (artesunate/ amodiaquine and artemether/ lumefantrine) and vice versa. Since these drugs are degraded using overlapping pathways in the liver, it is predicted that changes in both drug level and overall drug exposure will be observed.

Conditions

HIV Infections; Malaria

Keywords

Human Immunodeficiency Virus; Drug Interactions

Outcome Measures

Primary Outcomes (1)

• AUC (zero to infinity) of the antimalarial agent

  Each 3-day antimalarial treatment course throughout study

Study Arms (2)

Group A4

EXPERIMENTAL

healthy volunteers assigned to the efavirenz with artemether/lumefantrine intervention

Drug: efavirenz; Drug: artemether/lumefantrine

Group A3

EXPERIMENTAL

healthy volunteers assigned to the lopinavir/ritonavir with artemether/lumefantrine intervention

Drug: lopinavir/ritonavir; Drug: artemether/lumefantrine

Interventions

lopinavir/ritonavir DRUG

Two tablets of lopinavir 200mg / ritonavir 50mg orally twice daily with food for 26 days

Also known as: Kaletra

Group A3

efavirenz DRUG

One 600mg tablet orally once daily before bedtime on an empty stomach for 26 days

Also known as: Sustiva

Group A4

artemether/lumefantrine DRUG

4 tablets of artemether 20mg/lumefantrine 120mg twice daily with food. 2 three-day courses will be administered (with washout in between) during the duration of the trial.

Also known as: Coartem

Group A3; Group A4

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Absence of HIV infection prior to study entry
• Male or female aged 21-60 who are able to provide informed consent
• Subject is within 20% (+/-) of ideal body weight and weighs at least 50 kg.
• Healthy, without evidence of acute or chronic illness including diabetes, hypertension, CAD, psychiatric illnesses, renal or hepatic impairment.
• Screening laboratory tests that are normal or deemed not clinically significant by the study physician.
• Female subjects of reproductive potential must agree to the use of two forms of birth control methods for at least one month prior to study enrollment and for 6 weeks following study completion
• Female subjects must have a negative pregnancy test within 24 hours before receiving any study drugs.

You may not qualify if:

• Use of illicit drugs or alcohol that could interfere with the completion of the study
• Use of any over-the-counter or prescribed drugs unless approved by the principal investigator or study physician
• Use of drugs that are known to inhibit/induce CYP450 isozymes or are substrates of CYP3A4, CYP2D6, CYP2C8 enzymes (use of hormonal contraceptives is permitted).
• Pregnant or breastfeeding
• History of acute or chronic illnesses, such as diabetes, hypertension, CAD, psychiatric illnesses, renal or hepatic impairment.
• Evidence of acute illness
• Family history of congenital prolongation of QTc interval or with any conditions known to prolong QTc interval such as cardiac arrhythmias, bradycardia, or severe heart disease
• History of hypokalemia, hypomagnesemia, or hypercholesteremia

Sponsors & Collaborators

• Fran Aweeka: lead

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

HIV Infections; Malaria; Acquired Immunodeficiency Syndrome

Interventions

Lopinavir; lopinavir-ritonavir drug combination; efavirenz; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Francesca T Aweeka, PharmD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: June 2, 2008
• First Posted: June 16, 2008
• Study Start: July 1, 2005
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2010
• Last Updated: June 6, 2013

Record last verified: 2013-05

Locations

US (1)