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

This study has been completed.
Sponsor:
Information provided by:
OBEcure Ltd.
ClinicalTrials.gov Identifier:
NCT01168336
First received: July 20, 2010
Last updated: December 29, 2010
Last verified: December 2010
  Purpose

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


Condition Intervention Phase
Healthy
Drug: Betahistine standard formulation
Drug: Betahistine Extended Release formulation
Drug: Placebo
Phase 1

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

Resource links provided by NLM:


Further study details as provided by OBEcure Ltd.:

Primary Outcome Measures:
  • Evaluation of safety of escalating doses of extended release and standard formulations of betahistine, as monotherapy and as adjunctive to olanzapine [ Time Frame: thisoutcome will be assssed 7 weeks after radomization. ] [ Designated as safety issue: Yes ]
    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.

  • Evaluation of drug-drug interactions and pharmacokinetic profiles of escalating doses of extended release and standard formulations of betahistine, as adjunctive to olanzapine [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Evaluation of pharmacokinetic profiles of escalating doses of extended release and standard formulations of betahistine, as monotherapy and as adjunctive to olanzapine [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: July 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: placebo Drug: Placebo
matching placebo

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01168336

Locations
Romania
Pierrel Research HP-RO
Arad, Romania
Pierrel Research HP-RO
Timisoara, Romania, RO-300244
Sponsors and Collaborators
OBEcure Ltd.
Investigators
Principal Investigator: Rodica Cinca, Prof MD Pierrel Research HP-RO
  More Information

No publications provided

Responsible Party: Mihaela Pisleaga, PIERREL RESEARCH HP-RO SRL
ClinicalTrials.gov Identifier: NCT01168336     History of Changes
Other Study ID Numbers: BET 216
Study First Received: July 20, 2010
Last Updated: December 29, 2010
Health Authority: Romania: National Medicines Agency

Keywords provided by OBEcure Ltd.:
betahistine olanzapine weight sleepiness
olanzapine induced weight gain and sleepiness

Additional relevant MeSH terms:
Olanzapine
Betahistine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Vasodilator Agents
Cardiovascular Agents
Histamine Agonists
Histamine Agents

ClinicalTrials.gov processed this record on October 01, 2014