Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000373976
Ethics application status
Approved
Date submitted
31/03/2011
Date registered
11/04/2011
Date last updated
29/11/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
Placebo-Controlled, Single and Multiple Ascending Dose Study of BMS-919373 in Healthy Subjects.
Scientific title
Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of BMS-919373 in Healthy Subjects.
Secondary ID [1] 259868 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 265456 0
Condition category
Condition code
Cardiovascular 265612 265612 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PART A: The treatment groups have been completed and subjects received a single dose of either 10 mg, 30 mg, and 100 mg of BMS-919373 or placebo.
Based on exposures from these subjects, the following doses are selected for the remainder of Part A of this study:
Treatment Group 4: Subjects will receive a single 30 mg oral dose of BMS-919373 or placebo (suspension), in Period 1, followed by a single 30 mg dose of BMS-919373 or placebo following the administration of 40 mg famotidine in Period 2, followed by a single 30 mg dose of BMS-919373 or placebo following the administration of a high fat breakfast in Period 3. There will be at least 5 days between each dose.
Treatment Groups 5: Subjects will receive a single 1 mg oral dose of BMS-919373 or placebo (solution).
Treatment Group 6: Subjects will receive a single 10 mg oral dose of BMS-919373 or placebo (solution) in Period 1 followed by a single 10 mg oral dose of BMS-919373 or placebo (suspension) in Period 2.
Treatment Group 7: Subjects will receive a single 100 mg oral dose (repeat of Panel 3, with extended sampling) of BMS-919373 or placebo (suspension formulation).
PART B: Eight healthy subjects will be assigned to each of up to 4 sequential dose treatment groups in the MAD. Each subject will be administered a daily oral dose of BMS-919373 or placebo for 14 days. The following doses will be studied:
Treatment Group 1: 3 mg loading dose (LD) on Day 1, followed by 1mg QD of BMS-919373 or placebo on Days 2-14 (solution).
Treatment Group 2: 30 mg LD on Day 1, followed by 10 mg QD of BMS-919373 or placebo on Days 2-14 (suspension).
Treatment Group 3: 90 mg LD on Day 1, followed by 30 mg QD of BMS-919373 or placebo on Days 2-14 (suspension). In this panel, 2 mg midazolam will be administered 2 days prior to the initial dose of BMS-919373and again on Day 15, within 5 minutes after receiving BMS-919373 or placebo.
Treatment Group 4: elderly subjects will be administered a 90mg LD + 30 mg MD of BMS-919373 or placebo (suspension).
Intervention code [1] 264289 0
Treatment: Drugs
Intervention code [2] 264290 0
Prevention
Comparator / control treatment
Placebo oral solution or suspension matching the active treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 262394 0
Assessment of the Safety and Tolerability of BMS-919373 following singel and multiple doses
Timepoint [1] 262394 0
This will be assessed by safety laboratory assessment at Screening, the day prior to treatment (Day -1), Day 2 and Day 21 in Part A and Screening, Day -1, Day 2,5,14 and 34 in Part B. Vital Signs will be taken at 1, 2, 4, 8, 12, 24, 48 and 72 hours following initial dosing and 4 and 12 hours following subsequent doses in part B. Subjects will also be monitored via telemetry for 24 hours following dosing on Day 1 for Part A and Days 1, 5 and 14 in Part B
Secondary outcome [1] 273693 0
Assessment of the Pharmacokinetics of BMS-919373.
Timepoint [1] 273693 0
In Part A, PK samplese will be taken at 0.25 hr, 0.5hr, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 144, 216, 288, 384 and 480 hours post dose. In Part B, PK samples will be collected at 0.25 hr, 0.5hr, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24hrs following the initial dose on Day 1; pre-dose samples will be collected on days 4, 6, 8, 10, 12; and following final dosing on Day 14, samples will be collected at 0.25 hr, 0.5hr, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 144, 288 and 480 hours post dose.
Secondary outcome [2] 273697 0
Assessment of the effect of a high fat meal on the pharmacokinetics of BMS-919373.
Timepoint [2] 273697 0
Measured in Panel 2 of the food effect/famotidine panel. Subjects will undergo pharmacokinetic assessments at the same time points as in the fasted panels, following administration of a high fat meal.
Secondary outcome [3] 273698 0
Assessment of the effect of famotidine on the pharmacokinetics of BMS-919373
Timepoint [3] 273698 0
Measured during Panel 3 of the food effect/famotidine panel. Subjects will undergo pharmacokinetic assessments at the same time points as in the fasted panels, following administration of a single oral dose of 40mg famotidine.
Secondary outcome [4] 273699 0
Assessment of the effect of BMS-919373 on CYP3A4 enzyme activity.
Timepoint [4] 273699 0
Measured during the Part B panel 3following a single dose of 2mg midazolam in addition to BMS-919373/placebo. Pharmacokinetics will be taken at the same time points as for other Part B dose panels.
Secondary outcome [5] 273700 0
Assessment of the effect of BMS-919373 on ECG intervals.
Timepoint [5] 273700 0
In Part A, ECGs will be taken at screening, at Day -1, 1, 2, 4, 6 hours post dose, Day 5, Day 7 and prior to discharge on Day 21. In Part B, ECGs will be taken at screening and Day -1. ECGs will be recorded at pre-dose and 1,2, 4 and 6 hours after dosing on Days 1,5 and 14

Eligibility
Key inclusion criteria
Healthy subjects: women and men, ages 18 to 45

Healthy elderly subjects: post-menopausal women and men greater than or equal to 65 years of age.

Body mass index (BMI) of 18 to 32kg/m2, inclusive.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Current or history of cardiovascular diseases.

Healthy young subjects: resting heart rate of less than 45 beats/min and greater than 90 beats/min at screening.

Healthy elderly subjects: Resting heart rate of less than 50 beats/min and greater than 90 beats/min at screening.

- QTcF greater than 450 msec at screening.

- Any clinical significant finding during pre-dose telemetry or ECG monitoring.

- Current or history of neurological diseases or mental disorders current or history of kidney diseases.

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)
Each study participant deemed eligible for the study will be assigned a sequential study number by the study staff.
The pharmacist will then assign treatment to each study number according to a computer generated randomisation schedule. The pharmacist is the only person with access to this schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomized Controlled Trial: participants are assigned to intervention groups by chance. The randomisation schedule is computer generated.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Suspended
Date of first participant enrolment
Anticipated
9/05/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
88
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 264745 0
Commercial sector/Industry
Name [1] 264745 0
Bristol-Myers Squibb
Country [1] 264745 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
P.O Box 4000
Princeton, NJ 08543-4000
Country
United States of America
Secondary sponsor category [1] 263870 0
None
Name [1] 263870 0
Address [1] 263870 0
Country [1] 263870 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266730 0
Alfred Human Research Ethics Committee
Ethics committee address [1] 266730 0
Ethics committee country [1] 266730 0
Australia
Date submitted for ethics approval [1] 266730 0
28/03/2011
Approval date [1] 266730 0
Ethics approval number [1] 266730 0

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

Contacts
Principal investigator
Name 32397 0
Address 32397 0
Country 32397 0
Phone 32397 0
Fax 32397 0
Email 32397 0
Contact person for public queries
Name 15644 0
Jeffery Wong
Address 15644 0
Nucleus Network
Level 5, 89 Commercial Road
Melbourne, VIC, 3004
Country 15644 0
Australia
Phone 15644 0
+61 3 9496 6729
Fax 15644 0
+61 3 9076 8940
Email 15644 0
[email protected]
Contact person for scientific queries
Name 6572 0
A/Prof Peter Hodsman
Address 6572 0
Nucleus Network
Level 5, 89 Commercial Road
Melbourne, VIC, 3004
Country 6572 0
Australia
Phone 6572 0
+61 3 9076 8960
Fax 6572 0
+61 3 9076 8940
Email 6572 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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