Evaluation of Co-Administration of Betahistine as Adjunctive to Olanzapine in Healthy Subjects

Evaluation of Safety, Drug-Drug Interactions and Pharmacokinetic Profiles of Co-Administration of Escalating Doses of Extended Release and Standard Formulations of Betahistine as Monotherapy and as Adjunctive to Olanzapine in Healthy Subjects

The study aims to evaluate the safety and pharmacokinetics of extended release and standard formulations of betahistine when administered as monotherapy and as compared to their safety and pharmacokinetics when co-administered with olanzapine and to determine potential dose limiting toxicities and/or drug-drug interactions affecting the pharmacokinetics or safety of either medication, with particular emphasis on somnolence and weight gain secondary to olanzapine treatment

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Betahistine standard formulation; Drug: Betahistine Extended Release formulation

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Romania
  • Arad, Romania
    • Pierrel Research HP-RO
  • Timisoara, Romania, RO-300244
    • Pierrel Research HP-RO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy subjects 18 to 45 years of age and Body Mass Index (BMI)in the range of 18.5 to 27.0
2. Male and females
3. If female - must be non-lactating and non-pregnant, as measured by negative urine pregnancy test, have no plans to become pregnant during the study and practicing appropriate birth control such as oral contraceptives (for at least 60 days ), implants, intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner, for the study duration
4. Signed written informed consent.
5. Willing and able to comply with study procedures (including reporting to the research center for all weekday evening administrations and staying overnight in the research facility for required PK samplings

Exclusion Criteria:

1. Has a known intolerance, sensitivity or any contraindication to Betahistine or Olanzapine, as delineated in product label
2. Requires chronic or as needed use of systemic antihistamines, anti-obesity agents or psychoactive drugs .
3. Has had a significant body weight loss of over 4 kg in the 90 days prior to screening.
4. Has recently started a smoking cessation program.
5. Has screening ESS score of over 6.
6. Has personal history of gestational diabetes, or has a first degree relative with diabetes.
7. Has any clinically significant abnormality at screening, as judged by Investigator, in laboratory test values (chemistry, hematology, metabolic or urinalysis), including Fasting blood glucose level over 110 mg/dL or HBA1c over 6.0% at screening. Renal insufficiency defined as a serum creatinine over 1.5 mg/dL (133 µmol/L) at screening; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 ULN; Triglycerides [TG] >200 mg/dL or low-density lipoprotein cholesterol [LDL-C] >190 mg/dL), Thyroid-stimulating hormone (TSH) outside of the normal range;
8. Has any clinically significant abnormality in physical examination or electrocardiogram (ECG), as judged by the Investigator
9. Has a clinically significant history or presence of any disease or unstable medical condition that might be affected by enrollment to this trial, as judged by the Investigator, including; Cardiovascular or cerebrovascular disease Diabetes mellitus (type 1 or 2); Malignant disease within 5 years of screening; Polycystic ovary disease; Hypertension (sitting blood pressure >140/90 mmHg at screening or randomization), History of asthma symptoms in the past 5 years; History of peptic ulcers in the past 5 years; History of HIV, Hepatitis B or Hepatitis C
10. Plans on having any surgery (elective or otherwise) during the course of the study;
11. Has received any investigational drug within 90 days prior to screening.
12. Has been treated over the past 60 days, is currently treated, or is expected to require or undergo treatment with any medications for a period of more than 3 days (with the exception of antibiotic treatment for a period of less than 7 days).
13. Is an immediate family member of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site; or is employed by OBEcure Ltd.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Placebo; matching placebo
Experimental: betahistine; Betahistine 24 mg tablets	Drug: Betahistine standard formulation; betahistine 24 mg tablets
Experimental: betahistine XR; betahistine 32 mg tablets	Drug: Betahistine Extended Release formulation; betahistine 32 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of safety of escalating doses of extended release and standard formulations of betahistine, as monotherapy and as adjunctive to olanzapine	The total expected duration of the study for each subject will be 7 weeks. Total exposure time to Betahistine alone will be 1 week and total exposure time to Betahistine plus Olanzapine will be 3 weeks.	thisoutcome will be assssed 7 weeks after radomization.
Evaluation of drug-drug interactions and pharmacokinetic profiles of escalating doses of extended release and standard formulations of betahistine, as adjunctive to olanzapine		4 weeks
Evaluation of pharmacokinetic profiles of escalating doses of extended release and standard formulations of betahistine, as monotherapy and as adjunctive to olanzapine		4 weeks

Collaborators and Investigators

• Sponsor: OBEcure Ltd.
• Investigators: Principal Investigator: Rodica Cinca, Prof MD, Pierrel Research HP-RO

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: July 20, 2010
• First Submitted That Met QC Criteria: July 22, 2010
• First Posted (Estimate): July 23, 2010

Study Record Updates

• Last Update Posted (Estimate): December 30, 2010
• Last Update Submitted That Met QC Criteria: December 29, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: betahistine olanzapine weight sleepiness; olanzapine induced weight gain and sleepiness
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Histamine Agents; Histamine Agonists; Betahistine
• Other Study ID Numbers: BET 216