None listed
Conditions
Brief summary
This is an open-label, randomized, sequential dose-ascending cross-over study in healthy male adults. There will be three cohorts of subjects enrolled in this study, starting with Cohort 1. Each cohort will receive a different dose level of CTP-298. Prior to the start of the first period for each Cohort, subjects in that Cohort will be randomised to one of two treatments sequences: Sequence A: CTP-298 to ATV/ritonavir OR Sequence B: ATV/ritonavir to CTP-298 A total of 12 subjects will be enrolled into each cohort, with 6 subjects randomised to each sequence group within each cohort.
Interventions
There will be three cohorts of subjects enrolled in this study. Each cohort will receive a different dose level of CTP-298 as follows:
Cohort 1-CTP-298 450mg;
Cohort 2-CTP-298 550mg;
Cohort 3-CTP-298 650mg.
Prior to the start of the first period for each Cohort, subjects in that Cohort will be randomized to one of two treatment sequences:
Sequence A:CTP-298 (period 1) to ATV/ritonavir (period 2;
Sequence B: ATV/ritonavir (period 1) to CTP-298 (period 2).
Each sequence within each Cohort wil
There will be three cohorts of subjects enrolled in this study. Each cohort will receive a different dose level of CTP-298 as follows: Cohort 1-CTP-298 450mg; Cohort 2-CTP-298 550mg; Cohort 3-CTP-298 650mg. Prior to the start of the first period for each Cohort, subjects in that Cohort will be randomized to one of two treatment sequences: Sequence A:CTP-298 (period 1) to ATV/ritonavir (period 2; Sequence B: ATV/ritonavir (period 1) to CTP-298 (period 2). Each sequence within each Cohort will be treated in two 14-day periods, with an approximate 2 to 4 week washout (a minimum of 14 days) in-between treatments within each cohort. For each Cohort, if the first period of treatment is well-tolerated, then the second period of treatment will commence. Subject Procedures will remain the same for each period. Consented and qualified subjects will check-in to the site on the evening before dosing. Subjects will fast overnight for at least 10 hours prior to their morning breakfast. Following breakfast, each subject will receive their assigned treatment [either a daily dose of CTP-298 amorphous dispersion dosed as a suspension for 14 days or a dose of ATV 300 mg and a dose of ritonavir 100 mg (dosed as capsules) for 14 days]. Water consumption will be restricted for 1 hour before and 1 hour after dosing for Days 1 through 14; there will be no water restriction on any other study day. Meal times will be standardized throughout the study period, with a light meal (breakfast) being served around 7:30 AM, lunch around noon, afternoon snack around 4 PM, dinner around 6 PM and a late night snack around 10 PM. Blood samples (4 mL each) for pharmacokinetics will be collected at specified times as follows: Day 1: Predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 18, 24; Days 9, 10, 11, 12, 13: Pre-dose (within 5 minutes before AM dosing); Day 14: Predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, 18, 24, 28, 32, 36, and 48 h. Safety assessments will be based on continuous monitoring of AEs and periodic 12-lead ECGs and vitals. Additional safety assessments will include laboratory testing at specified time points and continuous monitoring of adverse events. Note that 7 days following the completion of the last period for a subject, an End of Study Visit will occur, at which a physical examination, vital signs, and clinical laboratories will be collected, as well as collection of adverse events.
Sponsors
CoNCERT Pharmaceuticals
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
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 investigator, 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. A subject with a non-clinically significant abnormality or laboratory parameters outside the reference range may be included only if the investigator considers that the finding will not compromise the subject’s safety and will not interfere with the study procedures or data interpretation. 2. Healthy adult males between 18 and 50 years of age, inclusive 3. Body weight > or = 50 kg and BMI within the range of 18 to 30 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. Willing and able to be confined at the clinical research center for the study days 6. Negative tests for selected drugs of abuse, cotinine, and alcohol at screening and Day -1 7. 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 (including nephrolithiasis), hepatic, or gastrointestinal (GI) conditions; or history of such conditions that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial, may interfere with the interpretation of safety and/or tolerability data obtained in the trial, or may interfere with the absorption, distribution, metabolism, or excretion of the study drugs 2. PR interval > or = 220 msec or QRS duration > or = 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. These laboratory tests may be repeated once, if they are abnormal on first screening, and if there is a medical reason to believe the results may be inaccurate. If the repeat test is within the reference range, the subject may be included only if the investigator considers that the previous finding will not compromise the subject’s safety and will not interfere with the interpretation of safety data. 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 greater than trace blood, 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; to be verified by a negative urine cotinine screen at screening and prior to the first dose of study drug 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. (The subject may take paracetamol (< or = 2 grams/day) or ibuprofen (< or = 1600 mg/day) for up to 48 hours prior to the first dose of study drug. If currently taking medications that are prescribed or recommended by a physician, no medication should be stopped for the purposes of study participation without agreement by that physician. 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 illness (ie, active infection) 17. Any other medical or psychiatric illness that could, in the investigator’s opinion, compromise the subject’s safety or interfere with the completion of this protocol. Subjects will be excluded from continuing into Period 2 of their Cohort if any of the following exclusion criteria are present based on the safety assessment prior to the start of Period 2: 1. PR interval > or = 220 msec or QRS duration > or = 120 msec or QT interval > 450 msec 2. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), serum creatinine, or bilirubin with a clinically significant abnormality, in the opinion of the Investigator 3. Urinalysis positive for greater than trace blood, protein or glucose 4. Any other clinically significant finding in the opinion of the investigator.
Outcome results
None listed