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

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.

Study Type: Interventional

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

Study Primary Completion Date: December 2003

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.

Intervention(s) in this Clinical Trial

• Drug: TAK-375, triazolam, alprazolam and placebo
  • TAK-375 16 mg, tablet, orally, one day only; TAK-375 80 mg, tablet, orally, one day only; TAK-375 160 mg, tablet, orally, one day only; triazolam 0.25 mg, capsule, orally, one day only; triazolam 0.50 mg, capsule, orally, one day only; triazolam 0.75 mg, capsule, orally, one day only; placebo, tablet, orally, one day only; placebo, capsule, orally, one day only; alprazolam 3 mg, liquid, orally, one day only

Arms, Groups and Cohorts in this Clinical Trial

• Other: 1.
  • TAK-375, triazolam, alprazolam and placebo (56 possible combinations total)

Primary Measures

• 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.
  • Time Frame: 7 to 8 Days
    Safety Issue?: Yes

Secondary Measures

• Subjective, reinforcing, behavioral, and cognitive effects as measured by Subject and Observer Rated Questionnaires.
  • Time Frame: 7 to 8 days
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Takeda Global Research & Development Center, Inc.

Overall Clinical Trial Officials and Contacts

Stephen Sainati, MD, PhD Study Director Takeda Global Research & Development Center, Inc.  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00671632

Study ID Number: 01-02-TL-375-015

ClinicalTrials.gov Identifier: NCT00671632

Health Authority: United States: Food and Drug Administration