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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01168336
• Other study ID #: BET 216
• Status: Completed
• Phase: Phase 1
• First received: July 20, 2010
• Last updated: December 29, 2010
• Start date: July 2010
• Est. completion date: December 2010

Study information

• Verified date: December 2010
• Source: OBEcure Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Romania: National Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Betahistine standard formulation
betahistine 24 mg tablets
• Betahistine Extended Release formulation
betahistine 32 mg tablets
• Placebo
matching placebo

Locations

Country	Name	City	State
Romania	Pierrel Research HP-RO	Arad
Romania	Pierrel Research HP-RO	Timisoara

Sponsors (1)

Lead Sponsor	Collaborator
OBEcure Ltd.

Country where clinical trial is conducted

Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Primary	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	Yes
Primary	Evaluation of pharmacokinetic profiles of escalating doses of extended release and standard formulations of betahistine, as monotherapy and as adjunctive to olanzapine		4 weeks	No