Placebo-Controlled Crossover Study to Evaluate Donepezil and MK-3134 for Reversal of Cognitive Impairment Associated With Scopolamine Administration (3134-005)(COMPLETED)

NCT01181310 | Completed Phase 1

• 2 other identifiers: 3134-0052007-001894-27
• Study Type: interventional
• Target: 31
• Locations: 0 countries
• Sites: N/A

Brief Summary

The drug, scopolamine, can result in short-term impairments of cognitive function, attention, and memory that resemble those seen in aging and Alzheimer's disease. This study tested the capability of both individual and combined doses of MK-3134 and the current standard treatment: donepezil (Aricept), to reverse such impairments, following a single dose of scopolamine. Participants were evaluated after each of 5 different treatment periods (in a cross-over, double-dummy design): A: placebo to match both donepezil (oral \[PO\]) and MK-3134 (PO) followed by placebo scopolamine (subcutaneous \[SQ\]); B: placebo to match both donepezil (PO) and MK-3134 (PO), followed by scopolamine SQ; C: MK-3134 (PO) followed by scopolamine SQ; D: donepezil (PO) followed by scopolamine SQ; E: MK-3134 (PO) and donepezil (PO) followed by scopolamine SQ. The doses of MK3134, donepezil, and scopolamine were the same over all treatment arms in which the specified drug was administered. There were 8 total visits for each treatment period, including 5 Treatment Visits requiring 14-day intervals between visits for study-drug washout. Participants were assessed for cognitive function before and after each treatment period during the Treatment Visits.

Conditions

Dementia

Keywords

dementia, cognitive impairment, neurodegeneration, Alzheimer's, acetylcholine, AchE

Outcome Measures

Primary Outcomes (1)

• CogState Early Phase Battery, Groton Maze Learning Test (GMLT) as measured by the number of errors on the GMLT over time (area under the GMLT-time curve) over hours 1-12.

  Participants learned a hidden pathway through a maze (10 x 10 grid of tiles on a computer touch screen) using step-by-step guess, with trial and error feedback after each step. Once the pathway was learned, participants repeated the same pathway four more times. The number of pathway errors was used to indicate the level of cognitive function.

  1, 2, 3, 4, 6, 8, and 12 hours relative to administration of SQ scopolamine or SQ placebo

Study Arms (10)

A, B, D, E, C

EXPERIMENTAL

Participants received treatment A, B, D, E, C for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

B, C, E, A, D

EXPERIMENTAL

Participants received treatment B, C, E, A, D for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

C, D, A, B, E

EXPERIMENTAL

Participants received treatment C, D, A, B, E for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

D, E, B, C, A

EXPERIMENTAL

Participants received treatment D, E, B, C, A for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

E, A, C, D, B

EXPERIMENTAL

Participants received treatment E, A, C, D, B for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

A, C, B, E, D

EXPERIMENTAL

Participants received treatment A, C, B, E, D for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

B, D, C, A, E

EXPERIMENTAL

Participants received treatment B, D, C, A, E for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

C, E, D, B, A

EXPERIMENTAL

Participants received treatment C, E, D, B, A for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

D, A, E, C, B

EXPERIMENTAL

Participants received treatment D, A, E, C, B for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

E, B, A, D, C

EXPERIMENTAL

Participants received treatment E, B, A, D, C for Periods 1, 2, 3, 4, and 5, respectively.

Drug: A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine; Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg; Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg; Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg; Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg

Interventions

A: Placebo to match Donepezil and MK-3134 + Placebo to match Scopolamine DRUG

Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.

A, B, D, E, C; A, C, B, E, D; B, C, E, A, D; B, D, C, A, E; C, D, A, B, E; C, E, D, B, A; D, A, E, C, B; D, E, B, C, A; E, A, C, D, B; E, B, A, D, C

B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg DRUG

Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.

A, B, D, E, C; A, C, B, E, D; B, C, E, A, D; B, D, C, A, E; C, D, A, B, E; C, E, D, B, A; D, A, E, C, B; D, E, B, C, A; E, A, C, D, B; E, B, A, D, C

C: MK-3134 25 mg + Scopolamine 0.5 mg DRUG

A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.

A, B, D, E, C; A, C, B, E, D; B, C, E, A, D; B, D, C, A, E; C, D, A, B, E; C, E, D, B, A; D, A, E, C, B; D, E, B, C, A; E, A, C, D, B; E, B, A, D, C

D: Donepezil 10 mg + Scopolamine 0.5 mg DRUG

A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.

Also known as: Aricept (donepezil)

A, B, D, E, C; A, C, B, E, D; B, C, E, A, D; B, D, C, A, E; C, D, A, B, E; C, E, D, B, A; D, A, E, C, B; D, E, B, C, A; E, A, C, D, B; E, B, A, D, C

E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg DRUG

A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.

Also known as: Aricept (donepezil)

A, B, D, E, C; A, C, B, E, D; B, C, E, A, D; B, D, C, A, E; C, D, A, B, E; C, E, D, B, A; D, A, E, C, B; D, E, B, C, A; E, A, C, D, B; E, B, A, D, C

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

Participants were eligible for inclusion in the study who were: * Male between 18 and 40 years of age. * Non-smokers, in good health (as defined in protocol), and were willing to follow study-related procedures. Participants were not eligible for inclusion in the study if they: * Had a history of illness that, in the opinion of the study investigator or as specified in protocol, might confound the results of the study or posed an potential, additional risk to the participant if they were to participate in the study. * Were taking any medication (prescription, nonprescription, vitamin supplements or herbal, illicit or legitimate) except for acetaminophen. * Had a history of any significant head injury/trauma.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Cho W, Maruff P, Connell J, Gargano C, Calder N, Doran S, Fox-Bosetti S, Hassan A, Renger J, Herman G, Lines C, Verma A. Additive effects of a cholinesterase inhibitor and a histamine inverse agonist on scopolamine deficits in humans. Psychopharmacology (Berl). 2011 Dec;218(3):513-24. doi: 10.1007/s00213-011-2344-y. Epub 2011 Jun 7.

  PMID: 21644059 DERIVED

MeSH Terms

Conditions

Dementia; Cognitive Dysfunction; Nerve Degeneration; Pain

Interventions

Scopolamine; Donepezil

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2010
• First Posted: August 13, 2010
• Study Start: June 1, 2007
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: November 6, 2015

Record last verified: 2015-11