HIV-1
Conditions
Interventions
Product Name: Dexelvucitabine
Product Code: D-d4FC
Pharmaceutical Form: Capsule*
INN or Proposed INN: Dexelvucitabine
CAS Number: 134379-77-4
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. a) Male (at birth) subjects, between 16 years (or the legal age of consent, whichever is older) and 75 years of age, utilizing adequate contraceptive methods. b) Female (at birth) subjects between 16 years (or the legal age of consent, whichever is older) and 75 years of age. Women of childbearing potential may be enrolled following a negative serum pregnancy test. If participating in activity that could lead to pregnancy, women shall agree to use TWO forms of contraception as listed below (at least one must be a barrier method) while receiving protocol-specified medication and for 2 months after stopping the medication. • Condom (male or female) with or without a spermicidal agent • Diaphragm or cervical cap with spermicide • IUD • Hormonal-based contraception Women who are not of reproductive potential (documented to be surgically sterile or postmenopausal [defined as amenorrhea >1 year and follicle stimulating hormone {FSH} >30 mU/mL]) are eligible to be enrolled without a serum pregnancy test and will not be required to use contraception. 2. Subjects treated with a HAART regimen(s), including a minimum of 3 drugs, for at least 3 months and who have been on a stable HAART regimen for a minimum of 8 weeks prior to the Screening visit. The HAART regimen must also remain stable from the Screening visit until randomization on Day 0 in order for the subject to qualify for enrollment. 3. Demonstrate evidence of failure of at least 3 drug classes, defined as follows: a) Prior NRTI use and presence of one or more NRTI-resistance-conferring mutations, including mutations at RT amino acids 41L, 65R, 67N, 70R, 74V or 74I, 184V or 184I, 210W, 215Y or 215F, and/or 219Q or 219E. b) Presence of one or more NNRTI-resistance conferring mutations, including mutations at RT amino acids 100I, 101E or 101P, 103N, 106A or 106M, 188L, and/or 190A or 190S or 190E at Screening or documented to be present on a prior genotype OR documented evidence of prior NNRTI use of at least 2 months duration with viral load =1000 copies/mL after at least 2 months of treatment. c) Prior ritonavir-boosted PI use AND presence of one or more PI-resistance-conferring mutations, including mutations at protease amino acids 33F, 46I or 46L, 50V, 82A or 82F or 82T or 82S, 84V, and/or 90M. 4. Demonstrate a Screening plasma HIV RNA concentration of ?1000 copies/mL (Roche Amplicor HIV-1 Monitor® Test, v1.5 – Quantitative assay) and, in the expert judgment of the investigator, be failing the current regimen. 5. Be able and willing to provide written informed consent. 6. Be able and willing to comply, in the opinion of the investigator, with the requirements of this study. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Current or recent (5 X upper limit of normal (ULN) e) Serum lipase >1.5 X ULN f) Serum creatinine > 3.0 x ULN 12. Subjects who have received an HIV prophylactic or corrective vaccination within 6 months prior to the first dose of study medication. 13. Subjects who have received radiation therapy or cytotoxic chemotherapeutic agents and have not recovered from side effects prior to the first dose of study medication. 14. Subjects with RT mutations Q151M or T69SS on Screening genotype.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare the antiviral effect of a 200 mg DFC dose versus a 300 mg 3TC dose in addition to optimized background therapy (OBT) over 24 weeks and 48 weeks in treatment-experienced subjects who have failed and harbor virus with resistance mutations to NRTIs, PIs, and NNRTIs. • To assess the safety and tolerability of a 200 mg DFC dose in HIV-1 infected subjects. ;Secondary Objective: • To analyze the resistance profile of DFC by evaluating pre-existing mutations that predict failure and by identifying emerging resistance mutations at the time of virologic failure of a regimen. • To evaluate the potential for lipoatrophy by comparing the rate of loss of limb fat between treatment groups by Dual Energy X-ray Absorptiometry (DEXA) scanning after 24, 48, and 96 weeks of therapy at selected treatment centers. • To evaluate the population pharmacokinetic (PK) parameters of DFC and 3TC. ;Primary end point(s): • Percent of subjects with =1.0 log10 decrease in viral load from Baseline to Week 24 based on non-completer equals failure (NC=F). • Percent of subjects at 48 weeks with sustained suppression of viral load =1.0 log10 below baseline as determined by time-to loss of virological response (TLOVR). | — |
Countries
United Kingdom
Outcome results
None listed