Scopolamine Challenge Study

• Detection Task (Speed; included in CogState Test Battery) [ Time Frame: Day 1 at 0, 5, 6, 7, 8, 10 and 12 hours of each period ] [ Designated as safety issue: No ]
• One Card Learning Task (Accuracy of performance; included in CogState Test Battery) [ Time Frame: Day 1 at 0, 5, 6, 7, 8, 10 and 12 hours of each period ] [ Designated as safety issue: No ]
• Continuous Paired Associate Learning Task (Number of errors; included in CogState Test Battery) [ Time Frame: Day 1 at 0, 5, 6, 7, 8, 10 and 12 hours of each period ] [ Designated as safety issue: No ]
• Bond-Lader Visual Analog Scales (included in CogState Test Battery) [ Time Frame: Day 1 at 0, 5, 6, 7, 8, 10 and 12 hours of each period ] [ Designated as safety issue: No ]
• Identification Task (Speed; included in CogState Test Battery) [ Time Frame: Day 1 at 0, 5, 6, 7, 8, 10 and 12 hours of each period ] [ Designated as safety issue: No ]

• Detection Task (Speed) and Identification Task (Speed) [ Time Frame: 0-12 hours ] [ Designated as safety issue: No ]
• One Card Learning Task (Accuracy of performance) [ Time Frame: 0-12 hours ] [ Designated as safety issue: No ]
• Continuous Paired Associate Learning Task (Number of errors) [ Time Frame: 0-12 hours ] [ Designated as safety issue: No ]
• Bond-Lader (alertness, contentment, and calmness) [ Time Frame: 0-12 hours ] [ Designated as safety issue: No ]
• Adverse events (spontaneous and solicited) [ Time Frame: 0-14 days ] [ Designated as safety issue: Yes ]
• vital signs (blood pressure, pulse rate and body temperature, 12 lead ECGs intervals) [ Time Frame: 0-14 days ] [ Designated as safety issue: Yes ]
• Clinical safety laboratory tests (hematology, fasting blood chemistry and urinalysis) [ Time Frame: 0-14 days ] [ Designated as safety issue: Yes ]
• Physical examinations [ Time Frame: 0-14 days ] [ Designated as safety issue: Yes ]
• Pharmacokinetics: Cmax, tmax, AUC last, AUC (data permitting), t1/2 term (data permitting), CL/F (PF-05212377/donepezil; data permitting), and CL (scopolamine; data permitting) [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]

It is hypothesized that PF-05212377 (SAM-760) will reverse scopolamine induced cognitive impairments in healthy adults subjects.

Proof of mechanism

• Drug: Placebo
  Capsule, single dose, oral, 1 day
• Drug: Scopolamine
  injectable subcutaneous formulation, single dose, 1 day
• Drug: PF-05212377
  5 mg, PF-05212377, capsule, single dose, 1 day
• Drug: PF-05212377
  20 mg, capsule PF-05212377, single dose, 1 day
• Drug: scopolamine
  injectable subcutaneous formulation, single dose, 1 day
• Drug: PF-05212377
  60 mg PF-05212377, capsule, single dose, 1 day
• Drug: scopolamine
  injectable sub cutaneous formulation, single dose, 1 day
• Drug: Donepezil
  Tablet, 10mg, single dose, 1 day
• Drug: Scopolamine
  injectable sub cutaneous formulation, single dose, 1 day

• No Intervention: Placebo
  placebo, plus scopolamine 0.5 mg
  Interventions:

  • Drug: Placebo
  • Drug: Scopolamine
• Experimental: PF-05212377 5 mg, plus scopolamine 0.5 mg;
  Interventions:

  • Drug: PF-05212377
  • Drug: Scopolamine
• Experimental: PF-05212377 20 mg, plus scopolamine 0.5 mg;
  Interventions:

  • Drug: PF-05212377
  • Drug: scopolamine
• Experimental: PF-05212377 60 mg, plus scopolamine 0.5 mg;
  Interventions:

  • Drug: PF-05212377
  • Drug: scopolamine
• Active Comparator: donepezil 10 mg, plus scopolamine 0.5 mg.
  Interventions:

  • Drug: Donepezil
  • Drug: Scopolamine

Inclusion Criteria:

• Healthy male and/or female subjects of non child bearing potential (WONCBP) between the ages of 18 and 55 years, inclusive.
• Body Mass index (BMI) of between 17.5 to 30.5 kg/m2 inclusive; and a total body weight greater than or equal to 50 kg (110 lbs).

Exclusion Criteria:

• Presence or history of any disorder that may prevent the successful completion of the study.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.