Clinical trial NCT03310645: Repeat Doses of BAY 1817080 in Healthy Males & Proof of Concept in Chronic Cough Patients
Official title: Two-part, Double-blind, Placebo-controlled, Randomized, Parallel-group Study: (Part 1) in Healthy Male Volunteers to Assess Safety and Tolerability of Ascending Repeated Oral Doses of BAY1817080, Followed by (Part 2), Two-way Crossover Administration of Four Different Doses in Patients With Refractory Chronic Cough to Assess Safety, Tolerability and Efficacy for Proof of Concept
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cough
Keywords: Refractory chronic cough
healthy volunteers
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2017-10-16
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: Ascending multiple doses in healthy volunteers Part 2: Ascending doses within two-way crossover design in patients
Primary purpose: TREATMENT

Brief summary: To investigate the safety and tolerability of ascending repeated oral doses of BAY1817080 in healthy volunteers(Part1).

To investigate the safety, tolerability and efficacy of BAY1817080 in patients with refractory chronic cough(Part2).


Eligibility criteria: Inclusion Criteria:

Part 1

* Male; healthy according to complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12 lead ECG, clinical laboratory tests
* Age: 18-45 years (inclusive) at the first screening visit.
* Non-smoker for at least the past 6 months and with a pack year history of equal to or less than 5 years.
* Subjects who are sexually active and have not been surgically sterilized must agree to use two reliable and acceptable methods of contraception simultaneously when having sexual intercourse with women of childbearing potential (one method used by the subject and one method used by the partner) during the study and for 90 days after receiving the investigational medicinal product and not to act as sperm donor for 90 days after dosing. \[Acceptable methods of contraception include for example: (a) condoms (male or female) with or without a spermicidal agent, (b) diaphragm or cervical cap with spermicide, (c) intrauterine device, (d) hormone-based contraception.

Part 2:

* Age: \>18 years at the first screening visit
* Refractory chronic cough for at least one year:

  * that has been shown to be unresponsive to at least 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip or unexplained cough, and
  * for which no objective evidence of an underlying trigger can be determined after investigation.
* Score of \>40 mm on the Cough Severity visual analogue scale (VAS) at screening.
* For male patients:

Male patients who are sexually active and have not been surgically sterilized must agree to use two reliable and acceptable methods of contraception simultaneously (one method used by the study patient and one method used by the partner) during the study and for 90 days after receiving the investigational medicinal product and not to act as sperm donor for 90 days after dosing. \[Acceptable methods of contraception include for example: (a) condoms (male or female) with or without a spermicidal agent, (b) diaphragm or cervical cap with spermicide, (c) intrauterine device, (d) hormone-based contraception.

--For female patients: Confirmed post-menopausal woman (defined as exhibiting spontaneous amenorrhea for at least 12 months before screening or as exhibiting spontaneous amenorrhea for 6 months before screening with documented serum follicle-stimulating hormone (FSH) levels \> 40 mIU/mL) or Woman without childbearing potential based on surgical treatment at least 6 weeks before screening such as bilateral tubal ligation, bilateral oophorectomy with or without hysterectomy (documented by medical report verification) or Woman of childbearing potential that agrees to use two reliable and acceptable methods of contraception simultaneously (one method used by the study patient and one method used by the partner) during the study and for at least 10 days after the last dose. Acceptable methods of contraception include for example: (a)condoms (male or female) with or without a spermicidal agent (b)diaphragm or cervical cap with spermicide (c) intrauterine device (d)hormone-based contraception.

Exclusion Criteria:

Part 1

* Relevant diseases potentially interfering with the study's aims (e.g.respiratory diseases) within the four weeks before screening or between screening and randomization
* Any febrile illness within the four weeks before screening or between screening and randomization
* Medical history of hypogeusia/dysgeusia or the subject has a dysfunction in his/her ability to taste, as revealed by the taste disturbance questionnaire during screening and the pre dose procedures
* Use of any over-the-counter cough mixture within the 24 hours before screening

Part 2:

* FEV1 or FVC of less than 60% of predicted normal, at screening
* History of upper or lower respiratory tract infection or recent significant change in pulmonary status within the 4 weeks before baseline visit.
* Current smoking habit or history of smoking within the 6 months before the screening visit.
* History of smoking (at any time) for more than 20 pack-years in total (20 cigarettes per pack)

Primary outcomes:
measure: Frequency of treatment emergent adverse events in study part 1
timeFrame: Up to 5 weeks
measure: Severity of treatment emergent adverse events in study 1
timeFrame: Up to 5 weeks
measure: Frequency of treatment emergent adverse events in study part 2
timeFrame: Up to 12 weeks
measure: Severity of treatment emergent adverse events in study part 2
timeFrame: Up to 12 weeks
measure: 24-hour cough counts
timeFrame: At week 1 in period A
measure: 24 hour cough counts
timeFrame: At week 2 in period A
measure: 24 hour cough counts
timeFrame: At week 3 in period A
measure: 24 hour cough counts
timeFrame: At week 1 in period B
measure: 24 hour cough counts
timeFrame: At week 2 in period B
measure: 24 hour cough counts
timeFrame: At week 3 in period B
Secondary outcomes:
Other outcomes:
Locations:
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital
state: Tyne And Wear
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: West Midlands
city: Belfast
country: United Kingdom
facility: Queen's University
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: London
country: United Kingdom
facility: King's College Hospital - NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Friedrich C, Francke K, Gashaw I, Scheerans C, Klein S, Fels L, Smith JA, Hummel T, Morice A. Safety, Pharmacodynamics, and Pharmacokinetics of P2X3 Receptor Antagonist Eliapixant (BAY 1817080) in Healthy Subjects: Double-Blind Randomized Study. Clin Pharmacokinet. 2022 Aug;61(8):1143-1156. doi: 10.1007/s40262-022-01126-1. Epub 2022 May 28.
citation: Morice A, Smith JA, McGarvey L, Birring SS, Parker SM, Turner A, Hummel T, Gashaw I, Fels L, Klein S, Francke K, Friedrich C. Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study. Eur Respir J. 2021 Nov 18;58(5):2004240. doi: 10.1183/13993003.04240-2020. Print 2021 Nov.