Pharmacokinetic Profile of Betahistine With and Without Selegiline in Healthy Volunteers
Condition: Ménière's Disease
MeSH terms: Meniere Disease
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Betahistine dihydrochloride; Selegiline-hydrochloride
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Vasomotal; Selegiline-neuraxpharm
Intervention MeSH terms: Betahistine; Selegiline
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention 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)
Primary purpose: Treatment
Keywords: Betahistine-dihydrochloride; Selegiline-hydrochloride; MAO-B inhibitor