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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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Betahistine 48 mg TID; 08:00, 13:00 and 18:00 (144 mg/day total)and Olanzapine (10 mg/day) |
|
| Control | Active Comparator | Matching placebo TID; 08:00, 13:00 and 18:00 and Olanzapine (10 mg/day). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
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:
Exclusion Criteria:
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:
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).
Has received any investigational drug within 90 days prior to screening.
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IFE Human Pharmacology | Arad | Romania | ||||
| IFE Human Pharmacology |
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| ID | Term |
|---|---|
| D001621 | Betahistine |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Timișoara |
| Romania |