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Pharmacokinetic Profile of Betahistine With and Without Selegiline in Healthy Volunteers (PK-BesT)

Primary Purpose

Ménière's Disease

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Betahistine dihydrochloride
Selegiline-hydrochloride
Sponsored by
Ludwig-Maximilians - University of Munich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ménière's Disease focused on measuring Betahistine-dihydrochloride, Selegiline-hydrochloride, MAO-B inhibitor

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Diagnosis and main criteria for inclusion: Adult healthy volunteers, males and non-pregnant, non-breastfeeding woman with adequate contraception Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the trial: Healthy volunteers (age ≥ 18 years and ≤ 70 years) as determined by screening and Principal Investigator's judgement No intake of medication due to an illness Written informed consent of the subject Systolic blood pressure between 90 and 140 mmHg and diastolic blood pressure between 60 and 90 mmHg at screening PQ interval in the ECG between 0.12 s and 0.20 s Duration of the QRS complex between 0.06 s and 0.10 s QTc interval 440 ms or less Heart rate between 60 and 100 beats per minute Subjects with the ability to follow study instructions and likely to attend and complete all required visits Subjects presenting with any of the following exclusion criteria were not included in the trial: Subject is not able to give consent A condition in which repeated serum draws or injections pose more than minimal risk for the subjects, such as haemophilia, other severe coagulation disorders or significantly impaired venous access Participation in another study with an investigational drug or device within the last 30 days, prior participation in the present study, or planned participation in another trial Intake of medication due to an illness Subjects with a physical or psychiatric condition which at the investigator's discretion may put the subject at risk, may confound the trial results, or may interfere with the subject's participation in the clinical trial before participation in this study Current or planned pregnancy or breastfeeding woman Woman of childbearing potential who is not willing to use medically reliable methods of contraception for the entire study duration Intake of alcohol 24 hours before first IMP intake or during study participation Known or persistent abuse of medication, drugs or alcohol (positive test for alcohol or drugs) Known contraindications for Betahistine, such as bronchial asthma, pheochromocytoma, treatment with antihistaminic drugs, ulcer of the stomach or duodenum, severe dysfunction of liver or kidney, hypersensitivity to Betahistine or other ingredients Known contraindications for Selegiline, e.g. use of opioids, tricyclic antidepressants, sympathomimetics, non-selective MAOIs, (selective) serotonin (-noradrenaline) re-uptake inhibitors (SSRI/SNRI), serotonin agonists, hypersensitivity to Selegiline or other ingredients Hereditary intolerance to galactose, hereditary deficiency of lactose, glucose-galactose-malabsorption AV Block in the ECG Hypotonic or hypertonic subjects according to the criteria of the National Heart, Lung and Serum Institute (Hypertension > 90/140 mmHg, Hypotension < 90/60 mmHg)

Sites / Locations

  • Department of Neurology, Ludwig Maximilian University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Betahistine-dihydrochloride

Betahistine-dihydrochloride and Selegiline-hydrochloride

Arm Description

Subjects received single dosages of Betahistine (24 mg, 48 mg, 96 mg) orally for pharmacokinetic serum draw with at least two days between the different dosages.

Subjects were pre-treated with Selegiline (5 mg/day) orally for one week and treated continuously with Selegiline (5 mg/day) in combination with the single dosages of Betahistine (24 mg, 48 mg, 96 mg) orally with at least two days between the different dosages.

Outcomes

Primary Outcome Measures

Mean AUC of Betahistine
Mean AUC of Betahistine in serum after treatment of Betahistine alone or with Selegiline

Secondary Outcome Measures

Mean Half Life of Betahistine
Half Life of Betahistine following the administration of different Betahistine doses with and without Selegiline
Occurrence of adverse effects
Occurrence of adverse effects following the administration of different Betahistine doses with and without Selegiline

Full Information

First Posted
June 26, 2023
Last Updated
July 10, 2023
Sponsor
Ludwig-Maximilians - University of Munich
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1. Study Identification

Unique Protocol Identification Number
NCT05938517
Brief Title
Pharmacokinetic Profile of Betahistine With and Without Selegiline in Healthy Volunteers
Acronym
PK-BesT
Official Title
Pharmacokinetic Profile of Betahistine Serum Concentration With and Without Selegiline in Healthy Volunteers - a Prospective Mono-center Open-labeled Phase I Trial ("PK-BeST")
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
June 2, 2021 (Actual)
Primary Completion Date
October 14, 2021 (Actual)
Study Completion Date
October 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ludwig-Maximilians - University of Munich

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this pharmakokinetic trial is to demonstrate that Betahistine serum concentration is higher after combination treatment with Betahistine and Selegiline compared to Betahistine alone. The main questions it aims to answer are: Is the plasma concentration of betahistine higher due to combination treatment with selegiline compared to betahistine monotherapy? How is the safety of the combination treatment with betahistine and selegiline, the pharmacokinetics of betahistine in different dosages in blood, and the inter-individual differences in the metabolism? Subjects satisfying all selection criteria will receive three different dosages of Betahistine alone orally in ascending order (24 mg, 48 mg, 96 mg) in the first period. In the second period, subjects received Betahistine treatment as described for first period but after pre- and continuous treatment with 5 mg/ml Selegiline orally. Plasma concentration (namely the AUC0-240min) of betahistine will be measured before and 10, 30, 60, 90, 120, 180, 240 minutes after treatment with blood examinations. Safety parameters include assessment of adverse events, ECG, vital signs, laboratory measurements including kidney and liver function, full blood count and pregnancy and drug screening test.
Detailed Description
This study was an investigator-initiated (IIT) prospective mono-center open-labeled trial to demonstrate that Betahistine serum concentration is higher after combination treatment with Betahistine and Selegiline compared to Betahistine alone in healthy subjects. Subjects were screened for their eligibility to participate in the study. Each subject gave written informed consent before any study-related procedures were performed. Subjects satisfying all selection criteria were included in the open-labeled trial receiving 3 different dosages of Betahistine alone in ascending order (24 mg, 48 mg, 96 mg) in the first period. In the second period, subjects received Betahistine treatment as described for first period but after pre- and continuous treatment with 5 mg/ml Selegiline. Betahistine serum concentrations were measured over a period of 240 min at 8 time points (area under the curve, AUC0-240 min). Safety parameters included assessment of adverse events, ECG, vital signs, laboratory measurements including kidney and liver function, full blood count and pregnancy and drug screening test). Safety monitoring was conducted during every visit and assessment of vital parameter and adverse events were conducted 10, 30, 60, 90, 120, 180, and 240min after betahistine intake. The clinical trial was conducted in a hospital of maximum care with the possibility to consult a specialist for possible symptoms of an intoxication especially an anesthesiologist, cardiologist and neurologist 24 hours/7 days a week.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ménière's Disease
Keywords
Betahistine-dihydrochloride, Selegiline-hydrochloride, MAO-B inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Subjects satisfying all selection criteria were included in the open-labeled trial receiving 3 different dosages of Betahistine alone in ascending order (24 mg, 48 mg, 96 mg) in the first period. In the second period, subjects received Betahistine treatment as described for first period but after pre- and continuous treatment with 5 mg/ml Selegiline.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Betahistine-dihydrochloride
Arm Type
Experimental
Arm Description
Subjects received single dosages of Betahistine (24 mg, 48 mg, 96 mg) orally for pharmacokinetic serum draw with at least two days between the different dosages.
Arm Title
Betahistine-dihydrochloride and Selegiline-hydrochloride
Arm Type
Experimental
Arm Description
Subjects were pre-treated with Selegiline (5 mg/day) orally for one week and treated continuously with Selegiline (5 mg/day) in combination with the single dosages of Betahistine (24 mg, 48 mg, 96 mg) orally with at least two days between the different dosages.
Intervention Type
Drug
Intervention Name(s)
Betahistine dihydrochloride
Other Intervention Name(s)
Vasomotal
Intervention Description
Each subject received single dosages of Betahistine (24 mg, 48 mg, 96 mg) for pharmacokinetic serum draw with at least two days between the different dosages.
Intervention Type
Drug
Intervention Name(s)
Selegiline-hydrochloride
Other Intervention Name(s)
Selegiline-neuraxpharm
Intervention Description
In the second period, each subject was pre-treated with Selegiline (5 mg/day) for one week and treated continuously with Selegiline (5 mg/day) in combination with the single dosages of Betahistine (24 mg, 48 mg, 96 mg) with at least two days between the different dosages.
Primary Outcome Measure Information:
Title
Mean AUC of Betahistine
Description
Mean AUC of Betahistine in serum after treatment of Betahistine alone or with Selegiline
Time Frame
240 minutes
Secondary Outcome Measure Information:
Title
Mean Half Life of Betahistine
Description
Half Life of Betahistine following the administration of different Betahistine doses with and without Selegiline
Time Frame
240 minutes
Title
Occurrence of adverse effects
Description
Occurrence of adverse effects following the administration of different Betahistine doses with and without Selegiline
Time Frame
up to 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Diagnosis and main criteria for inclusion: Adult healthy volunteers, males and non-pregnant, non-breastfeeding woman with adequate contraception Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the trial: Healthy volunteers (age ≥ 18 years and ≤ 70 years) as determined by screening and Principal Investigator's judgement No intake of medication due to an illness Written informed consent of the subject Systolic blood pressure between 90 and 140 mmHg and diastolic blood pressure between 60 and 90 mmHg at screening PQ interval in the ECG between 0.12 s and 0.20 s Duration of the QRS complex between 0.06 s and 0.10 s QTc interval 440 ms or less Heart rate between 60 and 100 beats per minute Subjects with the ability to follow study instructions and likely to attend and complete all required visits Subjects presenting with any of the following exclusion criteria were not included in the trial: Subject is not able to give consent A condition in which repeated serum draws or injections pose more than minimal risk for the subjects, such as haemophilia, other severe coagulation disorders or significantly impaired venous access Participation in another study with an investigational drug or device within the last 30 days, prior participation in the present study, or planned participation in another trial Intake of medication due to an illness Subjects with a physical or psychiatric condition which at the investigator's discretion may put the subject at risk, may confound the trial results, or may interfere with the subject's participation in the clinical trial before participation in this study Current or planned pregnancy or breastfeeding woman Woman of childbearing potential who is not willing to use medically reliable methods of contraception for the entire study duration Intake of alcohol 24 hours before first IMP intake or during study participation Known or persistent abuse of medication, drugs or alcohol (positive test for alcohol or drugs) Known contraindications for Betahistine, such as bronchial asthma, pheochromocytoma, treatment with antihistaminic drugs, ulcer of the stomach or duodenum, severe dysfunction of liver or kidney, hypersensitivity to Betahistine or other ingredients Known contraindications for Selegiline, e.g. use of opioids, tricyclic antidepressants, sympathomimetics, non-selective MAOIs, (selective) serotonin (-noradrenaline) re-uptake inhibitors (SSRI/SNRI), serotonin agonists, hypersensitivity to Selegiline or other ingredients Hereditary intolerance to galactose, hereditary deficiency of lactose, glucose-galactose-malabsorption AV Block in the ECG Hypotonic or hypertonic subjects according to the criteria of the National Heart, Lung and Serum Institute (Hypertension > 90/140 mmHg, Hypotension < 90/60 mmHg)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Strupp, M.D.
Organizational Affiliation
LMU Munich
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, Ludwig Maximilian University
City
Munich
State/Province
Bavaria
ZIP/Postal Code
81377
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

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Pharmacokinetic Profile of Betahistine With and Without Selegiline in Healthy Volunteers

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