Evaluation of Safety, Drug-Drug Interactions and Pharmacokinetic Profiles of Co-Administration of Betahistine With Olanzapine in Healthy Female Subjects

NCT00852956 | Completed Phase 1

• 1 other identifier: OBE 209
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

This will be a phase I, randomized, two-arm, double-blind, placebo-controlled, sequential study in up to 50 healthy female subjects. The study will be comprised of three treatment periods for a total of 4 weeks treatment duration: Period I 1 week (Days 1-7) administration of betahistine daily (three times per day; 144 mg/day total) or matching placebo. Period II 1 week (Days 8-14) titration of olanzapine once daily (2.5 to 10 mg) and continuation of betahistine or matching placebo administration (daily; three times per day) Period III 2 weeks (Days 15-28) of continued co-administration of betahistine/matching placebo, three times per day, and olanzapine once daily (7.5 to 10 mg/day)

Conditions

Healthy

Keywords

Betahistine; Olanzapine; Safety of co-administration of Betahistien and Olanzapine

Outcome Measures

Primary Outcomes (1)

• The primary objectives are to evaluate the safety, tolerability, pharmacokinetic profiles and drug-drug interactions of betahistine and olanzapine at steady-state in healthy female subjects.

  3 weeks

Study Arms (2)

Treatment

EXPERIMENTAL

Betahistine 48 mg TID; 08:00, 13:00 and 18:00 (144 mg/day total)and Olanzapine (10 mg/day)

Drug: Betahistine

Control

ACTIVE COMPARATOR

Matching placebo TID; 08:00, 13:00 and 18:00 and Olanzapine (10 mg/day).

Drug: Betahistine

Interventions

Betahistine DRUG

The study will be comprised of three treatment periods for a total of 4 weeks treatment duration: Period I 1 week (Days 1-7) administration of betahistine 48 mg three times daily (144 mg/day total) or matching placebo Period II 1 week (Days 8-14) titration of olanzapine once daily (from 2.5 mg up to 10 mg) and continuation of betahistine or matching placebo administration (three times daily as in Period I) Period III 2 weeks (Days 15-28) of co-administration of betahistine or matching placebo (three times daily; as in Periods II and III) and olanzapine once daily (7.5 or 10 mg, as tolerated) On Day 1, after a 7-day screening period, eligible subjects will be randomized to one of the two treatment groups in a 1:1 ratio: Betahistine 48 mg TID; 08:00, 13:00 and 18:00 (144 mg/day total) Matching placebo TID; 08:00, 13:00 and 18:00

Control; Treatment

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy female subjects 18 to 45 years of age.
• Signed written informed consent.
• Willing and able to comply with study procedures (including staying overnight in the research facility for required period for PK sampling).
• Regular menstrual period.
• All subjects should be non-lactating, have a negative urine pregnancy test result, and do not plan on become pregnant during the study, must practice or be willing to continue to practice appropriate birth control (such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner) during the entire study duration.
• Has been on a stable treatment regimen with any of the following medications for a minimum of 90 days prior to screening:
• Hormone replacement therapy;
• Oral contraceptives.

You may not qualify if:

• Has abnormal body composition, either overweight or obesity (BMI \> 27 Kg/m2) or undernourishment (BMI \< 18.5 Kg/m2).
• Has had a significant body weight loss of \>4 kg in the 90 days prior to screening.
• Pregnancy or lactation.
• Has recently started a smoking cessation program.
• Has known sensitivity to betahistine or olanzapine.
• Having first degree relatives with diabetes.
• Personal history of gestational diabetes.
• Subjects diagnosed with polycystic ovary disease.
• Has a clinically significant history or presence of any of the following conditions:
• Active or past history of cardiovascular or cerebrovascular disease including unstable angina, myocardial infarction, transient ischemic attacks/stroke, clinically significant arrhythmia, congestive heart failure, or cardiac valve abnormalities
• Diabetes mellitus (type 1 or 2)
• Fasting blood glucose level \> 100 mg/dL or HBA1c \> 6.0% at screening.
• Renal insufficiency defined as a serum creatinine \>1.5 mg/dL (133 µmol/L) at screening
• Malignant disease within 5 years of screening
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 ULN

Sponsors & Collaborators

• OBEcure Ltd.: lead

Study Sites (2)

IFE Human Pharmacology

Arad, Romania

Location

IFE Human Pharmacology

Timișoara, Romania

Location

MeSH Terms

Interventions

Betahistine

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 23, 2009
• First Posted: February 27, 2009
• Study Start: February 1, 2009
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: May 5, 2009

Record last verified: 2009-05

Locations

RO (2)