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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Dementia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01181310

3134-005

2007-001894-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

31 participants in 10 patient groups

A, B, D, E, C

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

B, C, E, A, D

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

C, D, A, B, E

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

D, E, B, C, A

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

E, A, C, D, B

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

A, C, B, E, D

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

B, D, C, A, E

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

C, E, D, B, A

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

D, A, E, C, B

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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

E, B, A, D, C

Experimental group

Description:

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

Treatment:

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

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

Drug: D: Donepezil 10 mg + Scopolamine 0.5 mg

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

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