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

NCT03310645 | Completed Phase 1

• 2 other identifiers: 181842017-001620-22
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 7

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

Keywords

Refractory chronic cough; healthy volunteers

Outcome Measures

Primary Outcomes (10)

• Frequency of treatment emergent adverse events in study part 1

  Up to 5 weeks

• Severity of treatment emergent adverse events in study 1

  The intensity of an AE is classified according to the following categories: * Mild: A type of adverse event that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. * Moderate: A type of adverse event that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. * Severe: A type of adverse event that requires intensive therapeutic intervention. The event interrupts usual activities of daily living, or significantly affects clinical status

  Up to 5 weeks

• Frequency of treatment emergent adverse events in study part 2

  Up to 12 weeks

• Severity of treatment emergent adverse events in study part 2

  The intensity of an AE is classified according to the following categories: * Mild: A type of adverse event that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. * Moderate: A type of adverse event that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. * Severe: A type of adverse event that requires intensive therapeutic intervention. The event interrupts usual activities of daily living, or significantly affects clinical status

  Up to 12 weeks

• 24-hour cough counts

  At week 1 in period A

• 24 hour cough counts

  At week 2 in period A

• 24 hour cough counts

  At week 3 in period A

• 24 hour cough counts

  At week 1 in period B

• 24 hour cough counts

  At week 2 in period B

• 24 hour cough counts

  At week 3 in period B

Study Arms (7)

Dose 1 of BAY1817080

EXPERIMENTAL

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

Drug: BAY1817080

Dose 2 of BAY1817080

EXPERIMENTAL

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

Drug: BAY1817080

Dose 3 of BAY1817080

EXPERIMENTAL

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

Drug: BAY1817080

Dose 4 of BAY1817080

EXPERIMENTAL

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

Drug: BAY1817080

Placebo

PLACEBO COMPARATOR

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

Drug: Matching Placebo

Placebo+BAY1817080

EXPERIMENTAL

Study Part 2: Randomized crossover design in cough patients Placebo+4 different doses of BAY1817080

Drug: BAY1817080; Drug: Matching Placebo

BAY1817080+Placebo

EXPERIMENTAL

Study Part 2: Randomized crossover design in cough patients 4 different doses of BAY1817080+Placebo

Drug: BAY1817080; Drug: Matching Placebo

Interventions

BAY1817080 DRUG

4 different doses over the course of study

BAY1817080+Placebo; Dose 1 of BAY1817080; Dose 2 of BAY1817080; Dose 3 of BAY1817080; Dose 4 of BAY1817080; Placebo+BAY1817080

Matching Placebo DRUG

Matching placebo for BAY1817080

BAY1817080+Placebo; Placebo; Placebo+BAY1817080

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bayer: lead

Study Sites (7)

North Tyneside General Hospital

North Shields, Tyne and Wear, NE29 8NH, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, West Midlands, B9 5SS, United Kingdom

Location

Queen's University

Belfast, BT9 7AB, United Kingdom

Location

Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

Location

King's College Hospital - NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

University Hospital of South Manchester

Manchester, M23 9LT, United Kingdom

Location

Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 38044419 DERIVED

• 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.

  PMID: 35624408 DERIVED

• 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.

  PMID: 33986030 DERIVED

Related Links

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

MeSH Terms

Conditions

Cough; Chronic Cough

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1: Ascending multiple doses in healthy volunteers Part 2: Ascending doses within two-way crossover design in patients

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 16, 2017
• Study Start: December 7, 2017
• Primary Completion: May 28, 2019
• Study Completion: June 19, 2019
• Last Updated: January 26, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (7)