A Phase Ib, Randomised, Placebo-Controlled, Double-Blind Study to Evaluate Potential Benefits of Two Concentrations of Betahistine Dihydrochloride Spray Administered as a Single Intranasal Dose in Adult Male and Female Volunteers with Eustachian Tube Dysfunctio

Phase 1

Completed

• Conditions: Rhinitis; Eustachian tube dysfunction; Allergic rhinitis (hay fever); Ear - Other ear disorders; Inflammatory and Immune System - Allergies

• Registration Number: ACTRN12615000657527
• Lead Sponsor: Otifex Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-25
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1.Male or female volunteers aged 18 years or older.
2.History of rhinitis and perceived ET dysfunction as defined by self-reported difficulty in equalising ears during plane flights, particularly descent and a history of allergic rhinitis (hay fever), but otherwise healthy as assessed by medical history and physical examination.
3.Body mass index between 18 and 30 kg/m2 (inclusive).
4. Healthy as assessed by medical history and physical examination.
5.A female participant is eligible to participate if she is of:
a. Non-childbearing potential defined as (1) having a documented tubal ligation at least 6 weeks prior to dosing; (2) having had a surgical bilateral oophrectomy (with or without hysterectomy); (3) at least 12 months of spontaneous amenorrhoea with follicle stimulating hormone (FSH) > 40 mIU/mL.
b. Child-bearing potential with negative urine pregnancy test at screening and negative urine pregnancy test at check-in (Day 1), AND:
* Agrees to abstain from sexual intercourse, or to use condoms plus one other acceptable form of contraception; i.e. intra-uterine device, hormonal contraception, or a female diaphragm, from the time of dosing until 4 weeks after dosing with study drug.
* OR has only same-sex partners, when this is her preferred and usual lifestyle.
6.Male participants with female partners of childbearing potential must agree to use condoms for the duration of the study and until 4 weeks after dosing with the study drug.
7.Normal (Type A) tympanometric measurements at screening consistent with the normal healthy adult population. Type A is defined as follows: Ear canal volume between 0.8-1.8 mL, compliance greater than 0.3 mL but less than 1.6 mL, middle ear pressure between -100 daPa and +100 daPa.
8.Capable of providing written informed consent.
9.Able to comply with study procedures and follow instructions from staff.

Exclusion Criteria

1.History or known presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic, ocular, or infectious disease; any acute infectious disease or signs of acute illness, especially of the ear, nose or throat (ENT) including Swimmer’s Ear”.
2.History of spontaneous pneumothorax, known lung bullae disease or known extensive lung scarring (risk of pulmonary barotrauma)
3.Any history or presence of recurrent OME (including childhood history), myringotomy tubes (grommets”), sinusitis, or known deviated nasal septum.
4.Presence of excessive cerumen (ear wax).
5.Positive pre-study test for alcohol or cotinine.
6.Presence or history of allergy to BH or any of the excipients or other allergy that, in the opinion of the investigator or Medical Monitor would compromise participation in the study.
7.Participant has received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
8.History of recurrent ENT infections, irritation or localised reaction to intranasally applied agents.
9.Recent history of liver disease, or known hepatic or biliary abnormalities with the exception of Gilbert’s syndrome or asymptomatic gallstones.
10.Females who are pregnant or breast-feeding.
11.Recent ENT surgery (within 3 months of screening).
12.History of bronchial asthma, gastric ulcers, or phaeochromocytoma.
13.History of migraines.
14.Use of prescription or non-prescription medications, vitamins, dietary or herbal supplements (including St John’s Wort) within 7 days prior to the dose of study drug unless in the opinion of the investigator and the Medical Monitor, the medication will not interfere with the study procedures or compromise participants safety.
15.Use of any cold and flu medication, antihistamine or nasal decongestants including but not limited to; Sudafed, Codral, Clarityne/Loratidine, Telfast, Drixine, etc within 7 days prior to the study dose.
16.A history of tobacco use in the last 3 months.
17.Current or history of symptomatic hypotension.
18.Any clinically significant deviation from normal in physical examination, vital signs or Electrocardiogram (ECG) beyond what is consistent with normal, healthy population.
19.Type As, Type Ad, Type B or Type C tympanometric measurements at screening and baseline as defined below:
a. Type A (not excluded): Ear canal volume in adults between 0.8-1.8 mL, compliance greater than 0.3 mL but less than 1.6 mL, middle ear pressure between -100 daPa and +100 daPa
b. Type As: shows same ear canal volume and middle ear pressure as Type A but the compliance (or peak) is equal to or less than 0.3 mL
c. Type Ad: shows same ear canal volume and middle ear pressure as Type A but the compliance (or peak) is equal to or greater than 1.6 mL
d. Type B: shows no measurable peak / middle ear compliance with any canal volume (low, normal or high)
e. Type C: shows a normal canal volume, a measurable peak, and middle ear pressure more negative than -100 daPa
20.A history of known hearing defects or tinnitus.
21.A participant who for whatever reason, in the opinion of the investigator, should not participate in the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Tympanometry assessments. Changes in ear pressure are measured via a tympanometric headsets.[Measurements are automatically made approximately every 3 minutes for 2 hours post-dose]

Secondary Outcome Measures

Name	Time	Method
To assess the tolerability of BH spray at total exposures of 4 mg and 40 mg compared with placebo as assessed by adverse events experienced.[Baseline, 2 hours post-dose, 7 days post-dose and at any time reported by the subject.]