None listed
Conditions
Brief summary
In this 2-part study, a total of 48 healthy male subjects will be enrolled and will be randomized to 1 of 8 sequences (4 in each study part), in groups of 4 subjects each. Part A of the study will be a 3-way crossover design. Part A1 will evaluate two single ascending doses of the single agent C-10276 (an ATV isotopolog), and a dose of Reyataz. Part A2 will evaluate the single agent C-10276 at two dose levels and co-administration of CTP-518 and C-10276. Part B will consist of two subparts. In the first subpart, C-10297 and C-10299 will be administered in 200 mg doses, in two groups of 4 subjects each. The second subpart consists of three groups of 8 subjects that will participate in a 3-way partial crossover study design. C-10297 and C-10299 will be administered in 400 and 600 mg doses, C-10276 will be administered in 600 mg and Reyataz will be dosed in 400 and 600 mg doses. All study drug doses, including the comparator, Reyataz, will be administered as single, open-labeled doses to subjects after a light meal. There will be a 7-day washout between individual subjects’ doses.
Interventions
Part A participants are permitted to participate in Part B of the study. Their participation is dependant upon availablility. Part A is divided into 3 periods. Each period is separated by a 7 day washout period. 16 Subjects are divided in to Group A1 and A2. Within each group 8 subjects will be randomised to recieve one of the following treatments. Group A1 the 8 subjects are separated into 2 groups of 4. For Period 1, 8 subjects receive C-10276 200mg. For Period 2, 4 subjects will receive C-102
Part A participants are permitted to participate in Part B of the study. Their participation is dependant upon availablility. Part A is divided into 3 periods. Each period is separated by a 7 day washout period. 16 Subjects are divided in to Group A1 and A2. Within each group 8 subjects will be randomised to recieve one of the following treatments. Group A1 the 8 subjects are separated into 2 groups of 4. For Period 1, 8 subjects receive C-10276 200mg. For Period 2, 4 subjects will receive C-10276 400mg and 4 subjects will receive Reyataz 400mg. For Period 3 the treatment will crossover and the 4 subjects receiving C-10276 400mg in Period 2 will receive Reyataz 400mg and the 4 subjects receiving Reyataz 400 mg in Period 2 will recieve C-10276 400mg. Group A2 the 8 subjects are separated into 2 groups of 4. For Period 1 8 subjects receive C-10276 300mg. For Period 2, 4 subjects will receive C-10276 400mg and 4 subjects will receive Co-Dose Ratio 1 CTP-518 (100mg): C-10276 (300mg). For Period 3 the treatment will crossover and the 4 subjects receiving C-10276 400mg in Period 2 will receive Co-dose ratio 1 and the 4 subjects receiving Co-dose ratio 1 in Period 2 will recieve C-10276 400mg. Part B is divided in to two sub-parts. The first sub-part consists of two Groups B1 and B2, each group consists of 4 subjects. 4 subjects will receive C-10297 (200 mg) and 4 subjects will receive C-10299 (200 mg). The second sub-part will consist of three groups, B3, B4 and B5. Each group will consist of 8 subjects. These subjects will be dosed over 3 periods. Each period is separated by a 7 day washout period. For Period 1, 8 subjects will receive C-10297 (400 mg), 8 subjects will receive C-10299 (400 mg) and 8 subjects will receive C-10276 (600 mg). For Period 2, all 3 groups of 8 subjects will receive Reyataz (400 mg). For Period 3, 8 subjects will receive C-10297 (600 mg), 8 subjects will receive C-10299 (600 mg) and 8 subjects will receive Reyataz (600 mg). All the Isotopologs will be administered via oral suspension. Reyataz will be administered via oral capsules.
Sponsors
Concert Pharmaceuticals, Inc
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy, as determined by the responsible physician, based on a medical evaluation including history, physical examination, vital signs, electrocardiograms (ECGs) and laboratory tests assessed at the screening visit and prior to the first dose of study drug. 2. Healthy adult males between 18 and 50 years of age, inclusive 3. Body weight greater than or equal to 50 kg and BMI within the range of 18 to 32 kg/m2, inclusive, at screening 4. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and the protocol 5. Negative tests for selected drugs of abuse, cotinine, and alcohol at screening and Day -1 6. Dietary habits that fall within the range of normal, as determined by the investigator. Examples of unusual diets are liquid diets, protein-only diets, high fat-diets, or lowcarbohydrate diets. 8. Willingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; and if engaging in sexual intercourse with a female partner who could become pregnant, a willingness of male subjects to use a condom and spermicide, in addition to having the female partner use another form of contraception such as an intrauterine device, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation. This criterion must be followed from the time of first study drug administration until 30 days after the final administration of study drug.
Exclusion criteria
1. History of clinically significant central nervous system (eg, seizures), cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal (GI) conditions 2. PR interval = 220 msec or QRS duration = 120 msec or QT interval > 450 msec obtained at screening visit or prior to the first dose of study drug 3. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), serum creatinine, or bilirubin > upper limit of normal (ULN) at screening or prior to the first dose of study drug. 4. Positive blood screen for human immunodeficiency virus (HIV antibody), hepatitis B virus surface antigen, or hepatitis C virus antibody at screening 5. Urinalysis positive for protein or glucose (greater than trace findings of protein or glucose) at screening or prior to the first dose of study drug 6. History of drug abuse within 6 months of screening 7. History of any tobacco product use within 3 months prior to the study, 8. Participation in a clinical trial and receipt of an investigational medication or a new chemical entity within 30 days, 5 half-lives, or twice the duration of the biological effect of any medication (whichever is longer) prior to the first dose of current study drug 9. Use of prescription or non-prescription medications, including herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug, or use of St. John’s Wort within 14 days prior to the first dose of study drug. 10. Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, or red wine within 7 days prior to administration of study drug 11. Consumption of any caffeine and/or xanthine products (ie, coffee, tea, chocolate and caffeine containing sodas, colas, etc) within 48 hours prior to each dose of study drug and while confined at the clinical site 12. Donation of blood or blood products or blood collection in excess of 470 mL within 8 weeks prior to dosing 13. History of sensitivity to any of the study drugs or components thereof, or a history of medication allergy or other allergy that, in the opinion of the investigator, contraindicates study participation 14. Unwillingness to comply with protocol-specified lifestyle and/or dietary restrictions 15. Major surgery within 4 weeks of screening 16. Uncontrolled intercurrent illness (ie, active infection)
Outcome results
None listed