Effects of PF-06412562 on Value-based Decision-making in Healthy Individuals

University of Zurich (UZH)

Status and phase: Completed; Phase 1

Conditions: Decision Making

Treatments: Drug: Placebo; Drug: PF-06412562

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03181841

PHA-16-D1AGO-01

Details and patient eligibility

About

Numerous psychiatric and neurodegenerative diseases like schizophrenia, dependency on drugs of abuse, depression and Parkinson's disease are related to motivational and cognitive deficits in value-based decision making, which frequently persist even after a successful pharmacological treatment. According to current neurobiologic models, cortical dopamine D1 receptors play a crucial role in taking value-based decisions. In this study, it will be investigated whether value-based decisions in healthy volunteers can be improved by stimulation of D1-receptors. For this purpose, a newly developed dopamine D1-agonist will be used, which selectively increases the activities of frontal D1- and D5-receptors. In this double-blind, randomized, placebo-controlled study, the effects of different single doses of PF-06412562, a not yet licensed D1-agonist, on value-based decision making will be compared with placebo. The use of different dosage strengths will allow to investigate a potential relationship between the extent of activity of the D1-receptor and its influence on behavioral indices.

Therefore, four parallel groups will be investigated. Each participant takes in a single dose of either PF-06412562 in different doses or placebo. A screening exam will be carried out 1-3 weeks before the drug intake, and a follow-up examination will be carried out approx. 1 week after the drug intake. At all 3 visits in the study centre, several tests for the investigation of value-based decision making will be carried out.

Enrollment: 120 patients

Sex: All

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Informed Consent as documented by signature on the informed consent form

• Physically and psychiatrically healthy men and women

• Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days for females and 90 days for males after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children.

• Female subjects of non childbearing potential must meet at least one of the following criteria:

  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure or;
  • Achieved post menopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the post menopausal state.

• All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

• Aged 18-35 years

• Negative pregnancy test (see exclusion criteria)

• Normal or corrected-to-normal vision

Exclusion Criteria (selected):

• Pregnant female subjects; breastfeeding female subjects
• considered to be healthy based on an extensive pre-study screening including anamnesis, physical examination, laboratory investigations, vital signs, ECG, etc.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 4 patient groups, including a placebo group

Active dose 1

Experimental group

Description:

Single dose of PF-06412562 in low dosage strength

Treatment:

Drug: PF-06412562

Active dose 2

Experimental group

Description:

Single dose of PF-06412562 in medium dosage strength

Treatment:

Drug: PF-06412562

Active dose 3

Experimental group

Description:

Single dose of PF-06412562 in higher dosage strength

Treatment:

Drug: PF-06412562

Placebo

Placebo Comparator group

Description:

Single dose of placebo

Treatment:

Drug: Placebo