Obstructive Sleep Apnea (OSA) Treated With a Potassium Channel Inhibitor (SANDMAN)

Randomized, Multi-center, Double-blind, Placebo-controlled, Group-comparison Study to Investigate Safety, Tolerability and Pharmacodynamics of BAY2253651 After Administration of a Single Nasal Dose in 60 Subjects With Obstructive Sleep Apnea and Open Exploratory Evaluation of Safety and Local Tolerability of Repeated Doses in Patients

The aim of this study in subjects with obstructive sleep apnea is to investigate pharmacodynamics, safety and tolerability after a single nasal administration of BAY2253651 and to evaluate first safety and tolerability of multiple dosing over 5 consecutive nights in OSA patients.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Drug: BAY2253651; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital Zurich
• United Kingdom
  • Oxford, United Kingdom, OX9 3DU
    • Oxford University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects need to be diagnosed with OSA (obstructive sleep apnea) but should be otherwise healthy at the discretion of the investigator.
• Patients must be pretreated with CPAP (continuous positive airway pressure) for OSA for at least 3 months before randomization.
• AHI of 15-50 per hour after 48 hours of CPAP withdrawal documented by baseline PSG (polysomnography, evaluated by the site staff) and at least 4 hours of total sleep time. (One retesting allowed).
• Female subjects must be of non-childbearing potential, i.e. post-menopausal (no menses for at least 1 year prior to randomization) or surgically sterile (tubal ligation, hysterectomy or bilateral oophorectomy)
• Men of reproductive potential together with their female partner(s) must agree to use at least two adequate contraception methods when sexually active. This applies for the time period between signing of the informed consent form and 3 months after the last administration of study drug.

Acceptable methods of contraception include, but are not limited to, (i) condoms (male or female) with or without a spermicidal agent; (ii) diaphragm or cervical cap with spermicide; (iii) intra-uterine device; (iv) hormone-based contraception

• Only Part B: Patients having completed Part A and had valid PSG after dosing in Part A.

Exclusion Criteria:

• Inability to comply with planned study procedures or to comply with study protocol requirements; this includes completing required data collection and attending required follow up study visits.
• Neck circumference above/equal 44 cm.
• Not predominantly obstructive sleep apnea evidenced by baseline PSG.
• Severely impaired breathing within two days prior to randomization (e.g. acute nasal congestion during upper airway infection).
• Subject with known allergies or hypersensitivities to the study drugs (active substances or excipients of the preparations). Known severe respiratory tract allergies e.g. allergic asthma.
• Intake of a nasal decongestant during the intervention time (48 hours before visit 1 until end of visit 2).
• Use of any topical medication containing local anesthetics for nose and throat within 7 days before first investigational medicinal product (IMP) administration.
• Participation in another trial with an investigational drug within 30 days or 5 half-lives of the investigational drug, whichever is longer before first application of study drug or concomitant participation in another clinical study with investigational medicinal product(s).
• Any other condition, which would make the subject unsuitable for this study and will not allow participation for the full planned study period (e.g. active malignancy or other condition limiting life expectancy to less than 12 months)
• Known history of severe heart failure (NYHA 3-4) or severe COPD (GOLD 3-4).
• Heavy smoking, i.e. more than 20 cigarettes per day and/or unable to stop smoking during the stay in the sleep laboratory.
• Suspicion of drug or alcohol abuse.
• Regular daily consumption of more than 1 L of xanthine-containing beverages.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A single dose BAY2253651; Single dose BAY2253651	Drug: BAY2253651; 100 µg (500 µg/ml * 200 µl) BAY2253651 intranasally
Placebo Comparator: Part A single dose Placebo; Single dose matching placebo	Drug: Placebo; Matching Placebo dosing
Experimental: Part B multiple dose BAY2253651; Multiple dose BAY2253651 on 5 consecutive nights	Drug: BAY2253651; 100 µg (500 µg/ml * 200 µl) BAY2253651 intranasally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of responders, defined by reduction of apnoea-hypopnoea-index (AHI) from baseline by ≥ 50%	2 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment emergent adverse events (TEAEs)	Up to 7 days
Severity of treatment emergent adverse events (TEAEs)	Up to 7 days

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Gaisl T, Turnbull CD, Weimann G, Unger S, Finger R, Xing C, Cistulli PA, West S, Chiang AKI, Eckert DJ, Stradling JR, Kohler M. BAY 2253651 for the treatment of obstructive sleep apnoea: a multicentre, double-blind, randomised controlled trial (SANDMAN). Eur Respir J. 2021 Nov 18;58(5):2101937. doi: 10.1183/13993003.01937-2021. Print 2021 Nov.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2018
• Primary Completion (Actual): May 23, 2019
• Study Completion (Actual): September 2, 2019

Study Registration Dates

• First Submitted: June 21, 2018
• First Submitted That Met QC Criteria: July 19, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Obstructive sleep apnea; Polysomnography; PSG; Potassium channel blocker
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: 19038; 2017-001851-29 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No