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Trial registered on ANZCTR


Registration number
ACTRN12611001058965
Ethics application status
Approved
Date submitted
10/10/2011
Date registered
11/10/2011
Date last updated
11/10/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
An open-labeled, randomized, crossover, multi-dose study in healthy male subjects to test the pharmacokinetics (how your body handles the drug e.g. how it absorbs it and how it eliminates it), safety, and tolerability of investigational drugs taken, with a pharmacokinetics comparison to the combination of the marketed drug Reyataz (Registered Trademark) and Norvir (Registered Trademark)
Scientific title
A Phase 1 Single Center, Open-Label, Randomized, Sequential Dose-Ascending Cross-Over Study to Evaluate the Pharmacokinetics and Tolerability of CTP-298 Amorphous Dispersion (450 mg, 550 mg, and 650 mg) at Steady State Compared to Atazanavir (300 mg) Coadministered With Ritonavir (100 mg) at Steady State in Healthy Male Adults
Secondary ID [1] 273186 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
NIL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment of HIV 278935 0
Condition category
Condition code
Infection 279117 279117 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 269513 0
Treatment: Drugs
Comparator / control treatment
Reyataz (atazanavir sulfate) 300 mg Co-administered with Norvir (ritonavir) 100mg for 14 days.
Control group
Active

Outcomes
Primary outcome [1] 279758 0
To characterize the 24-hour pharmacokinetics profile of a single dose of CTP-298.
Timepoint [1] 279758 0
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.
Primary outcome [2] 279759 0
To determine time to steady state (up to Day 14) and to characterize the steady-state 48-hour PK profile of CTP-298.
Timepoint [2] 279759 0
Blood samples (4 mL each) for pharmacokinetics will be collected at specified times as follows: Days 9, 10, 11, 12, 13: Pre-dose (within 5 minutes before AM dosing).
Primary outcome [3] 279760 0
To compare those CTP-298 PK profiles to that of the steady-state (Day 14) atazanavir (ATV) 300 mg PK profile when ATV is co-administered with 100 mg ritonavir.
Timepoint [3] 279760 0
Blood samples (4 mL each) for pharmacokinetics will be collected at specified times as follows: 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.
Secondary outcome [1] 294388 0
To characterize the tolerability of 14 days of dosing with CTP-298.
Timepoint [1] 294388 0
12-lead ECGs and vitals (blood pressure, heart rate) will be performed on Days 1, 14: pre-dose (0), and 2.5 hours after dosing, Days 3, 7, and 10: 2.5 hours after dosing and Day 16 (prior to discharge).
Additional safety assessments will include periodic clinical laboratory testing and continuous monitoring of adverse events.
The following commonly occurring side effects were reported in the previous CTP-298 trials: headache, upper respiratory tract infection and side effects related to blood collection. These events would be expected in this trial. Subjects will be instructed to report Adverse Events (AEs) during the study and the clinical site staff will query them regarding AEs throughout the study. The Investigator will review all AEs reported by the subject from the signing of the consent form through completion of the final follow-up. The Investigator will follow up on the outcome of any AE until the event has resolved or stabilized.
Secondary outcome [2] 294389 0
To compare the tolerability of 14 days of dosing with CTP-298 to that of 14 days of dosing with ATV co-administered with ritonavir.
Timepoint [2] 294389 0
12-lead ECGs and vitals (blood pressure, heart rate) will be performed on Days 1, 14: pre-dose (0), and 2.5 hours after dosing, Days 3, 7, and 10: 2.5 hours after dosing and Day 16 (prior to discharge).
Additional safety assessments will include periodic clinical laboratory testing and continuous monitoring of adverse events.
The following commonly occurring side effects were reported in the previous CTP-298 trials: headache, upper respiratory tract infection and side effects related to blood collection. These events would be expected in this trial. Subjects will be instructed to report Adverse Events (AEs) during the study and the clinical site staff will query them regarding AEs throughout the study. The Investigator will review all AEs reported by the subject from the signing of the consent form through completion of the final follow-up. The Investigator will follow up on the outcome of any AE until the event has resolved or stabilized.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Within each Cohort, subjects will be randomized (in a ratio of 1:1) to one of two treatment sequences:
Sequence A: Period 1-CTP-298; Period 2-Atazanavir plus ritonavir
Sequence B: Period 1-Atazanavir plus ritonavir; Period 2-CTP-298
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
NIL
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/11/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 270007 0
Commercial sector/Industry
Name [1] 270007 0
CoNCERT Pharmaceuticals
Country [1] 270007 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
CoNCERT Pharmaceuticals
Address
99 Hayden Ave., Suite 500,
Lexington, MA 02421
Country
United States of America
Secondary sponsor category [1] 268987 0
None
Name [1] 268987 0
Address [1] 268987 0
Country [1] 268987 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271969 0
Bellberry Limited
Ethics committee address [1] 271969 0
Ethics committee country [1] 271969 0
Australia
Date submitted for ethics approval [1] 271969 0
31/08/2011
Approval date [1] 271969 0
30/09/2011
Ethics approval number [1] 271969 0
Application No: 2011-08-423

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33253 0
Address 33253 0
Country 33253 0
Phone 33253 0
Fax 33253 0
Email 33253 0
Contact person for public queries
Name 16500 0
Samantha Woolman
Address 16500 0
CPR Pharma Services Pty Ltd
Suite C
32 West Thebarton Rd
THEBARTON SA 5031
Country 16500 0
Australia
Phone 16500 0
+61 8 8125 1913
Fax 16500 0
+61 8 8354 3146
Email 16500 0
Samantha.Woolman@cprservices.com.au
Contact person for scientific queries
Name 7428 0
Ginny Braman
Address 7428 0
CoNCERT Pharmaceuticals
99 Hayden Ave., Suite 500 | Lexington, MA 02421
Country 7428 0
United States of America
Phone 7428 0
+1 (781) 674 5253
Fax 7428 0
+1 (781) 674 5353
Email 7428 0
gbraman@concertpharma.com

No information has been provided regarding IPD availability


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No Supporting Document Provided



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