Alzheimer's DiseasePhase 1NCT01454115
Study to Evaluate the Safety, Pharmacokinetics and Tolerability of BMS-708163
A Phase 1 study testing BMS-708163 (Gamma-Secretase Inhibitor) in people with Alzheimer's Disease, run by Bristol-Myers Squibb.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- BMS-708163 (Gamma-Secretase Inhibitor)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- No sites listed yet
- Study dates
- Jun 2007to Mar 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
None listed.
About this study
Official title: 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
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.
- Conditions
- Alzheimer's Disease
- Being tested
- BMS-708163 (Gamma-Secretase Inhibitor), Placebo matching BMS-708163
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 0.3 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 1.5 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 5.0 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 15.0 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 50 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 100 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 200 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 400 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Capsule, Oral, 50 mg, Once daily, once
BMS-708163 (Gamma-Secretase Inhibitor)Drug
Oral Solution, Oral, 800 mg, Once daily, once
Placebo matching BMS-708163Drug
Oral Solution, Oral, 0 mg, Once daily, once
Placebo matching BMS-708163Drug
Capsule, Oral, 0 mg, Once daily, once
| Study group | Role | What they receive |
|---|---|---|
| Panel 1: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: 18 to 45 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 2: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: 18 to 45 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 3: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: 18 to 45 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 4: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: 18 to 45 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 5: BMS-708163 or Placebo | Experimental | 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 Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 6: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: 18 to 45 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 7: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: 18 to 45 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 8: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: 18 to 45 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 9: BMS-708163 or Placebo | Experimental | Healthy, elderly male subjects (age: 60 years and greater) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 10: BMS-708163 or Placebo | Experimental | Healthy, elderly female subjects (age: 60 years and greater) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 11: BMS-708163 or Placebo | Experimental | Healthy male subjects (age: between 46 to 59 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 12: BMS-708163 or Placebo | Experimental | Healthy male and/or female subjects or subjects with MCI (age: between 60-74 years) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 13: BMS-708163 or Placebo | Experimental | Healthy male and/or female subjects or with AD or MCI (age: 75 years or greater) Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
| Panel 15: BMS-708163 or Placebo | Experimental | Healthy young male subjects Receives: Drug: BMS-708163 (Gamma-Secretase Inhibitor); Drug: Placebo matching BMS-708163 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within 28 days of dosing
Secondary outcomes (9)
Effects of BMS-708163 on cortisol and QT interval corrected for heart rate
Measured: Within 28 days of dosing
Effect of BMS-708163 on thyroid stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and lymphocyte subsets
Measured: Within 28 days of dosing
Bioavailability of BMS-708163 from a capsule formulation relative to a solution formulation
Measured: Within 28 days of dosing
Effect of food on the PK of BMS-708163 administered as a capsule formulation
Measured: Within 28 days of dosing
Maximum observed plasma concentration (Cmax) of BMS-708163
Measured: Within 28 days of dosing
Time of maximum observed plasma concentration (Tmax) of BMS-708163
Measured: 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
Measured: Within 28 days of dosing
Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-708163
Measured: Within 28 days of dosing
Plasma half-life (T-HALF) of BMS-708163
Measured: Within 28 days of dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2011 (estimated)
- Study startJun 2007
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01454115
- Sponsor's protocol ID
- CN156-001
- Status last verified
- Nov 2011
- First submitted
- 7 Oct 2011
- Last updated
- 21 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Tong G, Wang JS, Sverdlov O, Huang SP, Slemmon R, Croop R, Castaneda L, Gu H, Wong O, Li H, Berman RM, Smith C, Albright CF, Dockens RC. Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral gamma-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clin Ther. 2012 Mar;34(3):654-67. doi: 10.1016/j.clinthera.2012.01.022. Epub 2012 Feb 28.
PubMed 22381714
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01454115
- Acronym / sponsor ID
- CN156-001
- Conditions
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 18 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| Panel 1: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: 18 to 45 years) |
| Panel 2: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: 18 to 45 years) |
| Panel 3: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: 18 to 45 years) |
| Panel 4: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: 18 to 45 years) |
| Panel 5: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy 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 |
| Panel 6: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: 18 to 45 years) |
| Panel 7: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: 18 to 45 years) |
| Panel 8: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: 18 to 45 years) |
| Panel 9: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy, elderly male subjects (age: 60 years and greater) |
| Panel 10: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy, elderly female subjects (age: 60 years and greater) |
| Panel 11: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male subjects (age: between 46 to 59 years) |
| Panel 12: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male and/or female subjects or subjects with MCI (age: between 60-74 years) |
| Panel 13: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy male and/or female subjects or with AD or MCI (age: 75 years or greater) |
| Panel 15: BMS-708163 or Placebo | Experimental | Drug: BMS-708163 (Gamma-Secretase Inhibitor), Drug: Placebo matching BMS-708163Healthy young male subjects |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 0.3 mg, Once daily, once | Drug | Panel 1: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 1.5 mg, Once daily, once | Drug | Panel 2: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 5.0 mg, Once daily, once | Drug | Panel 3: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 15.0 mg, Once daily, once | Drug | Panel 4: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 50 mg, Once daily, once | Drug | Panel 10: BMS-708163 or Placebo, Panel 5: BMS-708163 or Placebo, Panel 9: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 100 mg, Once daily, once | Drug | Panel 6: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 200 mg, Once daily, once | Drug | Panel 7: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 400 mg, Once daily, once | Drug | Panel 8: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Capsule, Oral, 50 mg, Once daily, once | Drug | Panel 11: BMS-708163 or Placebo, Panel 12: BMS-708163 or Placebo, Panel 13: BMS-708163 or Placebo, Panel 5: BMS-708163 or Placebo |
| BMS-708163 (Gamma-Secretase Inhibitor)Oral Solution, Oral, 800 mg, Once daily, once | Drug | Panel 15: BMS-708163 or Placebo |
| Placebo matching BMS-708163Oral Solution, Oral, 0 mg, Once daily, once | Drug | Panel 10: BMS-708163 or Placebo, Panel 15: BMS-708163 or Placebo, Panel 1: BMS-708163 or Placebo, Panel 2: BMS-708163 or Placebo, Panel 3: BMS-708163 or Placebo, Panel 4: BMS-708163 or Placebo, Panel 5: BMS-708163 or Placebo, Panel 6: BMS-708163 or Placebo, Panel 7: BMS-708163 or Placebo, Panel 8: BMS-708163 or Placebo, Panel 9: BMS-708163 or Placebo |
| Placebo matching BMS-708163Capsule, Oral, 0 mg, Once daily, once | Drug | Panel 11: BMS-708163 or Placebo, Panel 12: BMS-708163 or Placebo, Panel 13: BMS-708163 or Placebo, Panel 5: BMS-708163 or Placebo |
Primary outcome
Safety and tolerability of Single doses of BMS-708163 in the range of 0.3 to 800 mg in the healthy subjects
Time frame: Within 28 days of dosing
Based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests
9 secondary outcomes
Effects of BMS-708163 on cortisol and QT interval corrected for heart rate
Time frame: Within 28 days of dosing
Effect of BMS-708163 on thyroid stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and lymphocyte subsets
Time frame: Within 28 days of dosing
Bioavailability of BMS-708163 from a capsule formulation relative to a solution formulation
Time frame: Within 28 days of dosing
Effect of food on the PK of BMS-708163 administered as a capsule formulation
Time frame: Within 28 days of dosing
Maximum observed plasma concentration (Cmax) of BMS-708163
Time frame: Within 28 days of dosing
Time of maximum observed plasma concentration (Tmax) of BMS-708163
Time frame: 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
Time frame: Within 28 days of dosing
Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-708163
Time frame: Within 28 days of dosing
Plasma half-life (T-HALF) of BMS-708163
Time frame: Within 28 days of dosing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2011.
- Derived from this study: PubMed 22381714Tong G, Wang JS, Sverdlov O, Huang SP, Slemmon R, Croop R, Castaneda L, Gu H, Wong O, Li H, Berman RM, Smith C, Albright CF, Dockens RC. Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral gamma-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clin Ther. 2012 Mar;34(3):654-67. doi: 10.1016/j.clinthera.2012.01.022. Epub 2012 Feb 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-708163 (Gamma-Secretase Inhibitor) in people with Alzheimer's Disease, run by Bristol-Myers Squibb.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of Single doses of BMS-708163 in the range of 0.3 to 800 mg in the healthy subjects (time frame: Within 28 days of dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01454115, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2011.