Dose Optimisation of Stavudine for the Treatment of HIV Infection

• Register: ClinicalTrials.gov
• Last refreshed on: 8 February 2016
• Main ID: NCT02670772
• Date of registration: 22/01/2016
• Prospective Registration: No
• Primary sponsor: Willem Daniel Francois Venter
• Public title: Dose Optimisation of Stavudine for the Treatment of HIV Infection D4T
• Scientific title: A Randomised, Double-Blind, Multi-Centre, Parallel-Group Phase 3b Study to Demonstrate Non-inferiority of Stavudine (20 mg Twice Daily) Compared With Tenofovir Disoproxil Fumarate (300 mg Once Daily) When Administered in Combination With Lamivudine and Efavirenz in Antiretroviral-Naive Patients Infected With HIV-1
• Date of first enrolment: July 2012
• Target sample size: 1077
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02670772
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

India, South Africa, Uganda

Contacts

• Name: Francois Venter, FCP (SA)
• Affiliation: Wits Reproductive Health & HIV Institute

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patient is male or female aged =18 years (upper limit of <65 years in India)

- Patient has a documented laboratory diagnosis of infection with HIV-1 (positive
enzyme-linked immunosorbent assay HIV-1 antibody test) at screening or from previous
records

- Patient has a life expectancy of =2 years in the opinion of the investigator

- Patient has a plasma HIV-1 RNA level >1000 copies/mL

- Patient has a plasma CD4 count = 350 cells/mm3 using standard flow cytometry.

- Patient has the following clinical chemistry and haematological laboratory results:

- Serum creatinine =1.5 mg/dL (133 µmol/L) and a calculated creatinine clearance
level =60 mL/min according to the Cockcroft-Gault formula

- Serum alanine aminotransferase <5 × upper limit of normal (ULN)

- Serum aspartate aminotransferase <5 × ULN

- Serum lipase =1.5 × ULN

- Total bilirubin =1.5 mg/dL (25 µmol/L) unless felt by clinician to be due to
Gilbert syndrome

- Haemoglobin =7.0 g/dLAbsolute neutrophil count =500/mm3

- Platelet count =50 000/mm3.

- Female patients of childbearing potential, including those who are less than 2 years
post-menopausal, must agree to, and comply with using a highly effective method of
birth control (eg, barrier contraceptives [condom or diaphragm with a spermicidal
gel], hormonal contraceptives [implants, injectable, combination oral contraceptives,
transdermal patches, or contraceptive rings], intrauterine devices, or sexual
abstinence) while participating in this study. In addition, all women of childbearing
potential must agree to continue to use birth control throughout the study until last
study visit Women Not of Childbearing Potential are women who are postmenopausal or
permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy).

- Women of Childbearing Potential (WOCBP) - Any female who has experienced menarche and
does not meet the criteria for "Women Not of Childbearing Potential".

- Patient has the ability to comprehend the full nature and purpose of the study, in
the opinion of the investigator, including possible risks and side effects, to
cooperate with the investigator, to understand verbal and written instructions, and
to comply with the requirements of the entire study

- Patient is informed of the full nature and purpose of the study, including possible
risks and side effects, given ample time and opportunity to read and understand this
information, and sign and date the written informed consent before inclusion in the
study

Exclusion Criteria:

- Patients who have previously received treatment with any form of antiretroviral
therapy, including preventing mother-to-child transmission regimens

- Patients who are taking and cannot discontinue the following prohibited concomitant
medications at least 1 week prior to the baseline visit and for the duration of the
study period:

- Any agents with significant nephrotoxic potential

- Probenecid

- Systemic chemotherapy agents

- Drugs that have significant interactions with EFV other than rifampicin
Administration of any of the above medications should be discontinued at least 1
week prior to the baseline visit and for the duration of the study period.

- Patients who are clinically unstable, in the investigator's opinion, should be
stabilized prior to inclusion into this study and their baseline concomitant
medications should be stable for at least 1 month (30 days) prior to enrolment. In
addition, investigators should not anticipate changing dose levels or medications for
the duration of the study. Patients who, in the investigator's opinion, require
HIV-related prophylaxis (such as cotrimoxazole) and/or other HIV-related treatments
(e.g. treatment for oral thrush, tuberculosis, etc) and who, in the investigator's
opinion are clinically stable may have such treatment initiated or discontinued
during the screening period. The 30-day waiting period will not apply to the latter.

- Patients who have a current history of drug or alcohol abuse that, in the opinion of
the investigator, may be an impediment to patient adherence to the protocol

- Patients who have a medical history or evidence of gastrointestinal malabsorption
syndrome, chronic nausea, or vomiting which may prevent patients receiving oral
medication

- Patients who have participated in a study with an investigational drug within 60 days
of screening or who are currently receiving treatment with any other investigational
drug or device

- Patients who are hepatitis B surface antigen positive

- Patients with symptomatic peripheral neuropathies

- Female patients who are currently pregnant or breastfeeding

- Female patients desiring pregnancy during the next 2 years

- Patients who have a strong likelihood of relocating far enough to make access to the
study site difficult



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Human Immunodeficiency Virus

Acquired Immune Deficiency Syndrome

Intervention(s)

Drug: Stavudine

Drug: Tenofovir Disoproxil Fumarate

Primary Outcome(s)

Number of participants with undetectable plasma HIV-1 RNA levels [Time Frame: Week 48]

Number of participants with adverse events related to treatment [Time Frame: Week 48]

Secondary Outcome(s)

Number of participants with abnormal fat distribution [Time Frame: Week 96]

Number of participants with abnormal Bone mineral density and fat distribution [Time Frame: Week 96]

Number of participants with abnormal Bone mineral density. [Time Frame: Week 96]

Number of patients with plasma HIV-1 RNA levels <200 copies [Time Frame: Week 96]

Secondary ID(s)

BMGF

WRHI001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bill and Melinda Gates Foundation