Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04236440




Registration number
NCT04236440
Ethics application status
Date submitted
21/01/2020
Date registered
22/01/2020
Date last updated
8/08/2022

Titles & IDs
Public title
Study on the Safety of Drug BAY2586116 and How it Works in Patients With Obstructive Sleep Apnea (a Sleep Disorder Caused by the Narrowing and Collapse of the Airway During Sleep) Including the Blood Level of the Drug and Effect of Its Doses and Routes of Administration
Scientific title
Proof-of-mechanism Single-center, Randomized, Double-blind, Placebo-controlled 2-way Crossover Study to Investigate Pharmacodynamics, Safety, Tolerability and Exposure of BAY 2586116 (Part A) and an Open-label Comparison of Different Application Modes for Single Nasal/Pharyngeal Dose Administrations (Part B and Part C) in 12 Participants With Obstructive Sleep Apnea
Secondary ID [1] 0 0
20732
Universal Trial Number (UTN)
Trial acronym
KOALA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep Apnea, Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BAY2586116 (A1)
Treatment: Drugs - Placebo (A2)
Treatment: Drugs - BAY2586116 (B1)
Treatment: Drugs - BAY2586116 (B2)
Treatment: Drugs - BAY2586116 (B3)
Treatment: Drugs - BAY2586116 (C)

Experimental: Part A: A1A2+Part B+Part C - Part A: Participants will receive a single dose administration of BAY2586116 (A1) in treatment period 1, and a single dose administration of placebo (A2) in treatment period 2.

Part B: After successfully completing Part A, participants will proceed to Part B of the study.

Participants will receive a single dose administration of BAY2586116 (B1) in treatment period 3.

Based on the result of the interim analysis there are two possible scenarios regarding mode of application and doses of BAY2586116 to be administered in treatment period 4: 1) a single dose administration of BAY2586116 (B2) Or 2) a single dose administration of BAY2586116 (B3).

Part C: Participants completing Part B will be invited to participate in an additional treatment period with a single dose BAY2586116 (C).

Experimental: Part A: A2A1+Part B+Part C - Part A: Participants will receive a single dose administration of placebo (A2) in treatment period 1, and a single dose administration of BAY2586116 (A1) in treatment period 2.

Part B: After successfully completing Part A, participants will proceed to Part B of the study.

Participants will receive a single dose administration of BAY2586116 (B1) in treatment period 3.

Based on the result of the interim analysis there are two possible scenarios regarding mode of application and doses of BAY2586116 to be administered in treatment period 4: 1) a single dose administration of BAY2586116 (B2) Or 2) a single dose administration of BAY2586116 (B3).

Part C: Participants completing Part B will be invited to participate in an additional treatment period with a single dose BAY2586116 (C).


Treatment: Drugs: BAY2586116 (A1)
160 µg BAY2586116 (nasal spray administration)

Treatment: Drugs: Placebo (A2)
Placebo matching BAY2586116 (nasal spray administration)

Treatment: Drugs: BAY2586116 (B1)
160 µg BAY2586116 (nasal drops)

Treatment: Drugs: BAY2586116 (B2)
80 µg BAY2586116 (nasal spray)

Treatment: Drugs: BAY2586116 (B3)
160 µg BAY2586116 (pharyngeal spray with direct endoscopic application via a nostril)

Treatment: Drugs: BAY2586116 (C)
160 µg BAY2586116 (pharyngeal spray with direct endoscopic application via a nostril). It is the same procedure as described under part B3.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Critical closing pressure (Pcritgs) of the upper airway (cmH2O) during sleep with a polysomnography
Timepoint [1] 0 0
From start of sleep to end of sleep of administration day (Day 1)
Secondary outcome [1] 0 0
Incidence of treatment-emergent adverse events (TEAEs)
Timepoint [1] 0 0
From first application of study intervention up to 2 days after end of treatment with study intervention in each period
Secondary outcome [2] 0 0
Severity of treatment-emergent adverse events (TEAEs)
Timepoint [2] 0 0
From first application of study intervention up to 2 days after end of treatment with study intervention in each period

Eligibility
Key inclusion criteria
* Participant must be 18 years of age or above at the time of signing the informed consent.
* Participants need to be diagnosed with OSA but should be considered otherwise healthy at the discretion of the investigator.
* Participants do not need to be on CPAP therapy at the time of the study. However, if they are on therapy, participants must commit to keep their treatment schedule constant during the study period, especially the night before each administration of study intervention. For participants on CPAP, this will be monitored objectively using the compliance chip within the CPAP devices.
* Female of non-child bearing potential or male.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

1. Female participants:

-- i. Participants of non-childbearing potential, i.e. post-menopausal (no menses for at least 1 year) or surgically sterile (documented history of tubal ligation, hysterectomy or bilateral oophorectomy).
2. Male participants:

* i. Male participants of reproductive potential must agree to utilize two reliable and acceptable methods of contraception simultaneously when sexually active. This applies for the time period between admission to the study site until 12 weeks after the last administration of the study intervention.

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.

* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
* Ability to understand and follow study-related instructions.
* The informed consent must be signed before any study specific tests or procedures are done. For Part C reconsent must be signed.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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).
* Any other condition which at the discretion of the investigator would make the participant unsuitable for participation in the 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).
* Use of any topical medication containing local anesthetics for nose and throat within 2 days before each administration of study intervention.
* Donation of more than 100 mL of plasma or equivalent volume of blood within 4 weeks or 500 mL whole blood within 3 months before study drug administration.
* Previous participation in this study.
* Participation in another clinical study with study intervention(s) within 90 days prior to first administration.
* Heavy smoking, i.e. more than 20 cigarettes per day.
* Light smokers who are unable to cease smoking for the duration of the inhouse phases of the study (i.e. Study day 1 in treatment periods 1, 2, 3 and 4).
* Drug or alcohol abuse.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/06/2021
Sample size
Target
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Adelaide Institute for Sleep Health - Bedford Park
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The researchers in this study want to learn how drug BAY2586116 works in patients with obstructive sleep apnea (OSA). OSA is a sleep disorder marked by breathing pauses during sleep due to repetitive obstructions of the upper airway. BAY2586116 is a new drug under development for the treatment of OSA. It blocks protein channels expressed on the surface of the upper airways in small mechanoreceptors (a type of molecule that sense and pass stimulus outside a cell on to the inside of the cell through mechanical gate on the surface of the cell). Thus, the negative pressure reflex alerting the brain of inspiration is triggered more easily leading to a stronger activation of throat muscles. This prevents narrowing or collapse of the upper airways during sleep which is one of the pathological key factors in OSA.

Researchers will study the effects of different routes of administration (drops into the nose, spray into the nose or throat or spray into the throat by endoscopy). Endoscopy allows the doctor to look at areas in the throat that cannot be seen with a mirror: a thin tube-like instrument is inserted through the nose to check and give the medication. Different doses of the test drug will be given.

They also want to find out if participants experience any medical problems during the study.

Patients participating in this study will undergo three study parts. After completing Part A and Part B, participants will be asked to join Part C. In Part A, participants will receive both the test drug and placebo (a placebo looks like the test drug but does not have any medicine in it); in Part B, participants will receive the test drug twice via different routes of administration (drops in nose and spray in nose or throat) and in Part C, the participants would receive the test drug once via spray in throat by endoscopy. The sleep of the participants will be monitored by medical equipment. Participants will be asked to visit the clinic 7 times in 14 weeks in total.
Trial website
https://clinicaltrials.gov/study/NCT04236440
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04236440