A Study of the Acute Behavioral and Subjective Effects of TAK-375

Condition(s) targeted: Drug Abuse

Intervention: TAK-375, triazolam, alprazolam and placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Takeda Global Research & Development Center, Inc.

Official(s) and/or principal investigator(s):
Stephen Sainati, MD, PhD, Study Director, Affiliation: Takeda Global Research & Development Center, Inc.

This study focused on the drug abuse potential of TAK-375 16 mg, TAK-375 80 mg and TAK-375 160 mg compared to triazolam 0. 25 mg, triazolam 0. 50 mg, triazolam 0. 75 mg, alprazolam and a placebo, each taken once over an eight day period in subjects with a history of polydrug abuse.

Official title: A Phase II, Randomized, Single Center, Double-Blind Study of the Acute Behavioral and Subjective Effects of TAK-375

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome: The primary objective of this study was to determine whether a non-sedating drug with hypnotic properties (TAK-375) has abuse potential in abusers/misusers of hypnotic or anxiolytic drugs.

Secondary outcome: Subjective, reinforcing, behavioral, and cognitive effects as measured by Subject and Observer Rated Questionnaires.

Detailed description: Subjects participating in the study received varying doses of TAK-375, triazolam, placebo and alprazolam during the double-blind treatment period (56 possible dosing combinations total). Alprazolam was given to determine whether or not a subject reported liking it greater than a placebo for a commonly abused sedative drug. Subjects did not receive study drugs on weekends, holidays or sick days. Subjects completed a series of questionnaires and inventories post treatment.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Women of childbearing potential had to be nonpregnant and nonlactating with a negative

serum HCG pregnancy test result prior to receiving any dose of study medication.

- The subject was in good health as determined by a physician (ie, via medical history

and physical examination).

- The subject had clinical laboratory evaluations (including clinical chemistry [fasted

for at least 8 hours], hematology, and complete urinalysis) within the reference range for the testing laboratory unless the results were deemed not clinically significant by the investigator or sponsor.

- The subject had a history of substance abuse or dependence, on a commonly abused

recreational psychoactive drug (e. g., benzodiazepines, cocaine, opiates cannabinoids) as determined by clinical interview. Subjects had to have reported use of a sedative agent recreationally at least once within the last year, with or without mood-altering drugs, for its intoxicating effects.

- The subject was free of any signs/symptoms of withdrawal from substances after

admittance to the research unit and prior to the first dose of study medication.

- The subject reported a liking for study medication given on Day -2 and liking was of

greater magnitude than the liking for study medication given on Day - 1.

Exclusion Criteria:

- The subject had a known hypersensitivity to TAK-375 or related compounds including

melatonin.

- The subject had a known hypersensitivity to benzodiazepines or related compounds.

- The subject had a current diagnosis of any type of physical drug dependence other than

nicotine or caffeine.

- Subjects with a positive hepatitis B surface antigen were excluded. Subjects with

anti-hepatitis B and anti-hepatitis B core antigen or anti-hepatitis C virus could have been included in the study.

- The subject had a positive human immunodeficiency virus antibody at Screening. Consent

and counseling were performed according to the site's Standard Operating Procedures.

- The subject had a diastolic blood pressure greater than 90 mm Hg or a systolic

pressure of greater than 140 mm Hg at Screening.

- The subject had a previous history of cancer, other than basal cell carcinoma, that

had not been in remission for at least 5 years prior to the first dose of study drug.

- The subject had a clinically significant abnormal finding on physical examination or

ECG. The subject had a clinically significant illness in the previous 30 days.

- The subject had a diagnosis of a serious psychiatric condition (eg, schizophrenia,

major depression) as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th.

- The subject was currently participating in another investigational study or had

participated in an investigational study within the past 30 days.

Baltimore, Maryland, United States

Starting date: June 2003
Ending date: December 2003
Last updated: May 2, 2008