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

• ClinicalTrials.gov Identifier: NCT03310645
• Recruitment Status: Completed
• First Posted: October 16, 2017
• Last Update Posted: January 26, 2023
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Cough	Drug: BAY1817080; Drug: Matching Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Part 1: Ascending multiple doses in healthy volunteers Part 2: Ascending doses within two-way crossover design in patients
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: double blind
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 7, 2017
• Actual Primary Completion Date: May 28, 2019
• Actual Study Completion Date: June 19, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose 1 of BAY1817080; Study Part 1: Oral dose 1 of BAY1817080 twice daily with a loading dose administered three times on Day 1	Drug: BAY1817080; 4 different doses over the course of study
Experimental: Dose 2 of BAY1817080; Study Part 1: Oral dose 2 of BAY1817080 twice daily with a loading dose administered three times on Day 1	Drug: BAY1817080; 4 different doses over the course of study
Experimental: Dose 3 of BAY1817080; Study Part 1: Oral dose 3 of BAY1817080 twice daily with a loading dose administered three times on Day 1	Drug: BAY1817080; 4 different doses over the course of study
Experimental: Dose 4 of BAY1817080; Study Part 1: Oral dose 4 of BAY1817080 twice daily with a loading dose administered three times on Day 1	Drug: BAY1817080; 4 different doses over the course of study
Placebo Comparator: Placebo; Study Part 1: Oral dose of matching placebo twice daily with a loading dose administered three times on Day 1	Drug: Matching Placebo; Matching placebo for BAY1817080
Experimental: Placebo+BAY1817080; Study Part 2: Randomized crossover design in cough patients Placebo+4 different doses of BAY1817080	Drug: BAY1817080; 4 different doses over the course of study; Drug: Matching Placebo; Matching placebo for BAY1817080
Experimental: BAY1817080+Placebo; Study Part 2: Randomized crossover design in cough patients 4 different doses of BAY1817080+Placebo	Drug: BAY1817080; 4 different doses over the course of study; Drug: Matching Placebo; Matching placebo for BAY1817080

Outcome Measures

Primary Outcome Measures :

1. Frequency of treatment emergent adverse events in study part 1 [ Time Frame: Up to 5 weeks ]
2. Severity of treatment emergent adverse events in study 1 [ Time Frame: Up to 5 weeks ]

   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
3. Frequency of treatment emergent adverse events in study part 2 [ Time Frame: Up to 12 weeks ]
4. Severity of treatment emergent adverse events in study part 2 [ Time Frame: Up to 12 weeks ]

   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
5. 24-hour cough counts [ Time Frame: At week 1 in period A ]
6. 24 hour cough counts [ Time Frame: At week 2 in period A ]
7. 24 hour cough counts [ Time Frame: At week 3 in period A ]
8. 24 hour cough counts [ Time Frame: At week 1 in period B ]
9. 24 hour cough counts [ Time Frame: At week 2 in period B ]
10. 24 hour cough counts [ Time Frame: At week 3 in period B ]

Eligibility Criteria

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

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)

Contacts and Locations

Locations

United Kingdom

North Tyneside General Hospital

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

Birmingham Heartlands Hospital

Birmingham, West Midlands, United Kingdom, B9 5SS

Queen's University

Belfast, United Kingdom, BT9 7AB

Castle Hill Hospital

Cottingham, United Kingdom, HU16 5JQ

King's College Hospital - NHS Foundation Trust

London, United Kingdom, SE5 9RS

University Hospital of South Manchester

Manchester, United Kingdom, M23 9LT

Medicines Evaluation Unit

Manchester, United Kingdom, M23 9QZ

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

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

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03310645
• Other Study ID Numbers: 18184; 2017-001620-22 ( EudraCT Number )
• First Posted: October 16, 2017
• Last Update Posted: January 26, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: There are no current plans to share data. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:

Refractory chronic cough; healthy volunteers

Additional relevant MeSH terms:

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory