Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043 in Healthy Subjects

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Healthy Adult Normals

Treatments: Drug: Antacid Buffer Predose Solution; Drug: Placebo matching with BMS-933043; Drug: BMS-933043

Study type: Interventional

Funder types: Industry

Identifiers

NCT01605994

CN171-002

Details and patient eligibility

About

Includes a placebo-controlled sequential, ascending multiple-dose panels (10 panels, 8 ascending doses, and 2 fixed Japanese Panels exploring safety, tolerability, and Pharmacokinetic (PK) measures

Enrollment: 115 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy subjects as determined by no clinically significant deviation from normal medical history, physical examination, ECGs and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2
• Normal Neurological Exam (LP subjects only: to rule out focal CNS lesions that would render LP unsafe)
• Men and women, ages 18 to 55 years, inclusive.
• Women who are not of childbearing potential (WOCBP) [ie, who are postmenopausal or surgically sterile] and men
• Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
• Women must not be breastfeeding
• Sexually active fertile men must use effective birth control if their partners are WOCBP throughout the study and for 90 days after last dose

Exclusion criteria

• Any significant acute or chronic medical illness
• Current or recent (within 3 months of study drug administration) gastrointestinal disease
• Any major surgery within 4 weeks of study drug administration
• Any gastrointestinal surgery that could impact upon the absorption of study drug
• Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration
• Blood transfusion within 4 weeks of study drug administration
• Inability to tolerate oral medication
• Inability to be venipunctured and/or tolerate venous access
• Smoking more than 1 cigarette/cigar per week, within 3 months prior to screening
• Regular daily use of nicotine products or Varenicline (Chantix® or Champix®) within 3 months prior to screening
• Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders (4th Edition) [DSM IV], Diagnostic Criteria for Drug and Alcohol Abuse
• History of cardiac arrhythmias, or palpitations associated with presyncope or syncope or history of unexplained syncope

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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115 participants in 11 patient groups

Panel 1:BMS-933043(2mg)/Placebo+Antacid Buffer Solution

Experimental group

Description:

BMS-933043 2 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 2:BMS-933043(5mg)/Placebo+Antacid Buffer Solution

Experimental group

Description:

BMS-933043 5 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 3:BMS-933043(10mg)/Placebo+Antacid Buffer Solution

Experimental group

Description:

BMS-933043 10 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 4:BMS-933043(25mg)/Placebo+Antacid Buffer Solution

Experimental group

Description:

BMS-933043 25 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 5:BMS-933043(50mg)/Placebo+Antacid Buffer Solution

Experimental group

Description:

BMS-933043 50 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days CSF sampling required

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 6:BMS-933043(100mg)/Placebo+Antacid Buffer Solution

Experimental group

Description:

BMS-933043 100 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 7:BMS-933043(200mg)/Placebo+Antacid Buffer Solution

Experimental group

Description:

BMS-933043 200 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 8:BMS-933043(25mg)/Placebo+Antacid Buffer Predose

Experimental group

Description:

MAD Phase: Japanese Subjects. Cerebrospinal fluid (CSF) sampling not required BMS-933043 25 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 9:BMS-933043(200mg)/Placebo+Antacid Buffer Predose

Experimental group

Description:

Japanese Subjects. CSF sampling not required. BMS-933043 200 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

Panel 10:BMS-933043(350mg)/Placebo+Antacid Buffer Predose

Experimental group

Description:

BMS-933043 350 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution

CSF Panel:BMS-933043(MTD)/Placebo+Antacid Buffer Predose

Experimental group

Description:

If Panel 5 does not run. CSF Sampling at steady state BMS-933043 maximum tolerated dose (MTD), solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days

Treatment:

Drug: Placebo matching with BMS-933043

Drug: BMS-933043

Drug: Antacid Buffer Predose Solution