Study to Evaluate the Safety, Pharmacokinetics and Tolerability of BMS-708163

Study Overview
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Brief Summary
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The primary objective is to assess the safety and tolerability of a single oral dose of BMS-708163 in healthy young male subjects and in elderly male and female subjects.

Official Title
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Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-708163 in Healthy Male Subjects and a Comparison to Elderly Male and Female Subjects

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: BMS-708163 (Gamma-Secretase Inhibitor)
* Drug: Placebo matching BMS-708163
* Drug: Placebo matching BMS-708163


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Panels 1- 8 and Panels 14-15: healthy male subjects between the ages of 18 to 45 Panels 9 and 10: healthy elderly males and females ages 60 and greater Panel 11: healthy males between the ages of 46-59 Panel 12: males and/or females either healthy or with mild cognitive impairment (MCI) between the ages of 60 and 74 Panel 13: males and/or females, healthy or with Alzheimer's disease (AD) or MCI that were 75 years of age or greater Acceptable medical history, physical examinations, vital signs, electrocardiograms, hemoccult stool tests, and clinical laboratory evaluations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel 1: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 0.3 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 2: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 1.5 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 3: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 5.0 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 4: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 15.0 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 5: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years). In Period 2: Subjects will receive BMS-708163 or placebo as a capsule formulation. In Period 3: Subjects will receive BMS-708163 or placebo as a capsule formulation within 5 minutes of consuming a standard high-fat breakfast on Day 1 | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 50 mg, Once daily, once<br>Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Capsule, Oral, 50 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Capsule, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 6: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 100 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 7: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 200 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 8: BMS-708163 or Placebo<br>Healthy male subjects (age: 18 to 45 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 400 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 9: BMS-708163 or Placebo<br>Healthy, elderly male subjects (age: 60 years and greater) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 50 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 10: BMS-708163 or Placebo<br>Healthy, elderly female subjects (age: 60 years and greater) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 50 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 11: BMS-708163 or Placebo<br>Healthy male subjects (age: between 46 to 59 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Capsule, Oral, 50 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Capsule, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 12: BMS-708163 or Placebo<br>Healthy male and/or female subjects or subjects with MCI (age: between 60-74 years) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Capsule, Oral, 50 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Capsule, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 13: BMS-708163 or Placebo<br>Healthy male and/or female subjects or with AD or MCI (age: 75 years or greater) | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Capsule, Oral, 50 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Capsule, Oral, 0 mg, Once daily, once<br>|
| Experimental: Panel 15: BMS-708163 or Placebo<br>Healthy young male subjects | Drug: BMS-708163 (Gamma-Secretase Inhibitor)<br>* Oral Solution, Oral, 800 mg, Once daily, once<br>Drug: Placebo matching BMS-708163<br>* Oral Solution, Oral, 0 mg, Once daily, once<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of Single doses of BMS-708163 in the range of 0.3 to 800 mg in the healthy subjects | Based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests | Within 28 days of dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of BMS-708163 on cortisol and QT interval corrected for heart rate |  | Within 28 days of dosing | 
| Effect of BMS-708163 on thyroid stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and lymphocyte subsets |  | Within 28 days of dosing | 
| Bioavailability of BMS-708163 from a capsule formulation relative to a solution formulation |  | Within 28 days of dosing | 
| Effect of food on the PK of BMS-708163 administered as a capsule formulation |  | Within 28 days of dosing | 
| Maximum observed plasma concentration (Cmax) of BMS-708163 |  | Within 28 days of dosing | 
| Time of maximum observed plasma concentration (Tmax) of BMS-708163 |  | Within 28 days of dosing | 
| Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-708163 |  | Within 28 days of dosing | 
| Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-708163 |  | Within 28 days of dosing | 
| Plasma half-life (T-HALF) of BMS-708163 |  | Within 28 days of dosing |