Clinical trial NCT03181841: Effects of PF-06412562 on Value-based Decision-making in Healthy Individuals
Official title: Effects of PF-06412562 on Value-based Decision-making in Healthy Individuals: a Mono-center, Randomized, Placebo Controlled, Double-blind Study (Phase I)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Decision Making
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2017-06-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Change from baseline in a delay discounting task.
timeFrame: 1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake.
measure: Change from baseline in a risk discounting task.
timeFrame: 1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake.
measure: Effect of PF-06412562 on an effort discounting task (compared to placebo).
timeFrame: 5 hours after drug intake.
measure: Effect of PF-06412562 on the Pavlovian to instrumental transfer task (compared to placebo).
timeFrame: 5 hours after drug intake.
measure: Effect of PF-06412562 on an exploration / exploitation task (compared to placebo).
timeFrame: 5 hours after drug intake.
measure: Effect of PF-06412562 on a probabilistic reversal learning task (compared to placebo).
timeFrame: 5 hours after drug intake.
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events (safety and tolerability of PF-06412562)
timeFrame: throughout the study and up to 1 week after study drug intake.
Other outcomes:
measure: Plasma concentrations of PF-06412562
timeFrame: blood sampling 4 hours and 8 hours after the study drug intake.
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Dept. of Clinical Pharmacology and Toxicology
Study officials:
affiliation: University of Zurich, Dept. of Economics
name: Philippe Tobler, Prof. Dr.
role: STUDY_DIRECTOR
affiliation: University of Zurich
name: Alexander Jetter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Soutschek A, Gvozdanovic G, Kozak R, Duvvuri S, de Martinis N, Harel B, Gray DL, Fehr E, Jetter A, Tobler PN. Dopaminergic D1 Receptor Stimulation Affects Effort and Risk Preferences. Biol Psychiatry. 2020 Apr 1;87(7):678-685. doi: 10.1016/j.biopsych.2019.09.002. Epub 2019 Sep 12.
citation: Soutschek A, Kozak R, de Martinis N, Howe W, Burke CJ, Fehr E, Jetter A, Tobler PN. Activation of D1 receptors affects human reactivity and flexibility to valued cues. Neuropsychopharmacology. 2020 Apr;45(5):780-785. doi: 10.1038/s41386-020-0617-z. Epub 2020 Jan 21.