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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01181310
First received: August 12, 2010
Last updated: November 21, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Dementia
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
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Five-Period, Placebo-Controlled, Crossover Study to Evaluate the Effect of Donepezil and MK-3134 on Reversal of Cognitive Impairment Associated With a Single-Dose of Scopolamine.

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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. [ Time Frame: 1, 2, 3, 4, 6, 8, and 12 hours relative to administration of SQ scopolamine or SQ placebo ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: June 2007
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A, B, D, E, C
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: B, C, E, A, D
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: C, D, A, B, E
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: D, E, B, C, A
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: E, A, C, D, B
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: A, C, B, E, D
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: B, D, C, A, E
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: C, E, D, B, A
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: D, A, E, C, B
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)
Experimental: E, B, A, D, C
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
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of placebo to match scopolamine SQ.
Drug: B: Placebo to match Donepezil and MK-3134 + Scopolamine 0.5 mg
Single doses of placebo to match both donepezil and MK-3134 PO, plus a single dose of scopolamine 0.5 mg SQ.
Drug: C: MK-3134 25 mg + Scopolamine 0.5 mg
A single dose of MK-3134 PO 25 mg, plus a single dose of scopolamine SQ 0.5 mg.
Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg
A single dose of donepezil 10 mg PO, plus a single dose of scopolamine 0.5 mg SQ.
Other Name: Aricept (donepezil)
Drug: E: Combo: Donepezil 10 mg + MK-3134 25 mg + Scopolamine 0.5 mg
A combination of single doses of all active drugs: donepezil 10 mg and MK-3134 25 mg PO, plus scopolamine, SQ.
Other Name: Aricept (donepezil)

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01181310     History of Changes
Other Study ID Numbers: 3134-005, 2007-001894-27
Study First Received: August 12, 2010
Last Updated: November 21, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Merck Sharp & Dohme Corp.:
dementia, cognitive impairment, neurodegeneration, Alzheimer's, acetylcholine, AchE

Additional relevant MeSH terms:
Cognition Disorders
Dementia
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Butylscopolammonium Bromide
Donepezil
Scopolamine Hydrobromide
Adjuvants, Anesthesia
Autonomic Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Mydriatics
Neurotransmitter Agents
Nootropic Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014