Repeat Doses of BAY 1817080 in Healthy Males & Proof of Concept in Chronic Cough Patients

NCT ID: NCT03310645

Last Updated: 2023-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-07
• Study Completion Date: 2019-06-19

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).

Conditions

Cough

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dose 1 of BAY1817080

Study Part 1:

Oral dose 1 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

4 different doses over the course of study

Dose 2 of BAY1817080

Study Part 1:

Oral dose 2 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

4 different doses over the course of study

Dose 3 of BAY1817080

Study Part 1:

Oral dose 3 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

4 different doses over the course of study

Dose 4 of BAY1817080

Study Part 1:

Oral dose 4 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

4 different doses over the course of study

Placebo

Study Part 1:

Oral dose of matching placebo twice daily with a loading dose administered three times on Day 1

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

Matching placebo for BAY1817080

Placebo+BAY1817080

Study Part 2:

Randomized crossover design in cough patients Placebo+4 different doses of BAY1817080

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

4 different doses over the course of study

Matching Placebo

Intervention Type: DRUG

Matching placebo for BAY1817080

BAY1817080+Placebo

Study Part 2:

Randomized crossover design in cough patients 4 different doses of BAY1817080+Placebo

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

4 different doses over the course of study

Matching Placebo

Intervention Type: DRUG

Matching placebo for BAY1817080

Interventions

BAY1817080

4 different doses over the course of study

Intervention Type: DRUG

Matching Placebo

Matching placebo for BAY1817080

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

North Tyneside General Hospital

North Shields, Tyne and Wear, United Kingdom

Birmingham Heartlands Hospital

Birmingham, West Midlands, United Kingdom

Queen's University

Belfast, , United Kingdom

Castle Hill Hospital

Cottingham, , United Kingdom

King's College Hospital - NHS Foundation Trust

London, , United Kingdom

University Hospital of South Manchester

Manchester, , United Kingdom

Medicines Evaluation Unit

Manchester, , United Kingdom

Countries

United Kingdom

References

Reif S, Schultze-Mosgau MH, Engelen A, Piel I, Denner K, Roffel A, Tiessen R, Klein S, Francke K, Rottmann A. Mass Balance and Metabolic Pathways of Eliapixant, a P2X3 Receptor Antagonist, in Healthy Male Volunteers. Eur J Drug Metab Pharmacokinet. 2024 Jan;49(1):71-85. doi: 10.1007/s13318-023-00866-0. Epub 2023 Dec 3.

Reference Type: DERIVED

PMID: 38044419 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35624408 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33986030 (View on PubMed)

Related Links

http://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

https://clinicaltrials.bayer.com/

Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Other Identifiers

2017-001620-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18184

Identifier Type: -

Identifier Source: org_study_id