Pharmacokinetic Profile of Betahistine With and Without Selegiline in Healthy Volunteers

NCT05938517 | Completed Phase 1

• 1 other identifier: 19-0992 fed
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Ménière's Disease

Keywords

Betahistine-dihydrochloride; Selegiline-hydrochloride; MAO-B inhibitor

Outcome Measures

Primary Outcomes (1)

• Mean AUC of Betahistine

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

  240 minutes

Secondary Outcomes (2)

• Mean Half Life of Betahistine

  240 minutes

• Occurrence of adverse effects

  up to 8 weeks

Study Arms (2)

Betahistine-dihydrochloride

EXPERIMENTAL

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.

Drug: Betahistine dihydrochloride

Betahistine-dihydrochloride and Selegiline-hydrochloride

EXPERIMENTAL

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.

Drug: Betahistine dihydrochloride; Drug: Selegiline-hydrochloride

Interventions

Betahistine dihydrochloride DRUG

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.

Also known as: Vasomotal

Betahistine-dihydrochloride; Betahistine-dihydrochloride and Selegiline-hydrochloride

Selegiline-hydrochloride DRUG

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.

Also known as: Selegiline-neuraxpharm

Betahistine-dihydrochloride and Selegiline-hydrochloride

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult healthy volunteers, males and non-pregnant, non-breastfeeding woman with adequate contraception
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

Department of Neurology, Ludwig Maximilian University

Munich, Bavaria, 81377, Germany

Location

Related Publications (1)

• Strupp M, Churchill GC, Naumann I, Mansmann U, Al Tawil A, Golentsova A, Goldschagg N. Examination of betahistine bioavailability in combination with the monoamine oxidase B inhibitor, selegiline, in humans-a non-randomized, single-sequence, two-period titration, open label single-center phase 1 study (PK-BeST). Front Neurol. 2023 Oct 18;14:1271640. doi: 10.3389/fneur.2023.1271640. eCollection 2023.

  PMID: 37920833 DERIVED

MeSH Terms

Conditions

Meniere Disease

Interventions

Betahistine; Selegiline

Condition Hierarchy (Ancestors)

Endolymphatic Hydrops; Labyrinth Diseases; Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Michael Strupp, M.D.

  LMU Munich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior physician

Model Details: 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.

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: July 10, 2023
• Study Start: June 2, 2021
• Primary Completion: October 14, 2021
• Study Completion: October 14, 2021
• Last Updated: July 12, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)