Repeat Doses of BAY1902607 in Healthy Males and Proof of Concept in Chronic Cough Patients

NCT03535168 | Completed Phase 1

• 2 other identifiers: 194302018-000129-29
• Study Type: interventional
• Target: 59
• Locations: 2 countries
• Sites: 8

Brief Summary

The primary objectives of this study:

• To investigate the safety and tolerability of ascending repeated oral doses of BAY1902607 in healthy subjects (Part 1).
• To investigate the effect of BAY1902607 on the pharmacokinetics (PK) of a sub-therapeutic 1 mg dose of midazolam (Part 1).
• To investigate the safety, tolerability and efficacy of BAY1902607 in patients with refractory chronic cough (Part 2).

Conditions

Cough

Keywords

Healthy volunteers

Outcome Measures

Primary Outcomes (7)

• Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 1

  Approximately 5 weeks

• Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 2

  Approximately 12 weeks

• AUC of midazolam without BAY1902607

  Part 1

  At Day -1

• AUC of midazolam in combination with BAY1902607

  Part 1

  At Day 13

• Cmax of midazolam in combination with BAY1902607

  Part 1

  At Day 13

• Cmax of midazolam without BAY1902607

  Part 1

  At Day -1

• Number of Coughs Experienced by the Patient Within a 24-hour Period (24- hour cough count/hour) in Part 2

  Part 2: Coughs monitored by VitaloJAK cough recorder (Vitalograph)

  24 hours

Study Arms (6)

Dose 1 of BAY1902607

EXPERIMENTAL

Part 1: From Day 1 until Day 12 the dose 1 of BAY1902607 will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, dose 1 of BAY1902607 will be given only once.

Drug: BAY1902607; Drug: Midazolam

Dose 2 of BAY1902607

EXPERIMENTAL

Part 1: From Day 1 until Day 12 the dose 2 of BAY1902607 will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, dose 2 of BAY1902607 will be given only once.

Drug: BAY1902607; Drug: Midazolam

Dose 3 of BAY1902607

EXPERIMENTAL

Part 1: From Day 1 until Day 12 the dose 3 of BAY1902607 will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, dose 3 of BAY1902607 will be given only once.

Drug: BAY1902607; Drug: Midazolam

Matching placebo

EXPERIMENTAL

Part 1: From Day 1 until Day 12 the matching placebo will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, matching placebo will be given only once.

Drug: Matching placebo; Drug: Midazolam

BAY1902607+Matching Placebo

EXPERIMENTAL

Part 2: Randomized crossover design in cough patients 4 different doses of BAY1902607+matching placebo

Drug: BAY1902607; Drug: Matching placebo

Matching Placebo+BAY1902607

EXPERIMENTAL

Part 2: Randomized crossover design in cough patients Matching placebo+4 different doses of BAY1902607

Drug: BAY1902607; Drug: Matching placebo

Interventions

BAY1902607 DRUG

3 different doses over the course of part 1 and 4 different doses over the course of part 2.

BAY1902607+Matching Placebo; Dose 1 of BAY1902607; Dose 2 of BAY1902607; Dose 3 of BAY1902607; Matching Placebo+BAY1902607

Matching placebo DRUG

Matching placebo for BAY1902607

BAY1902607+Matching Placebo; Matching Placebo+BAY1902607; Matching placebo

Midazolam DRUG

Part 1: The subjects will initially (Day -1) receive a sub-therapeutic dose of 1 mg midazolam as solution in the morning.

Dose 1 of BAY1902607; Dose 2 of BAY1902607; Dose 3 of BAY1902607; Matching placebo

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, heart rate), 12-lead ECG, clinical laboratory tests
• Age: 18-45 years (inclusive) at the first screening visit
• Non-smoker for at least 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, 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 treatment of cough according to the 2006 British Thoracic Society (BTS) guideline
• Score of ≥ 40 mm on the Cough Severity visual analogue scale (VAS) at screening
• 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 31 days (1 average menstrual cycle of 28 days plus approx. 5 half-lives of BAY 1902607) after the last dose. In addition during the study and for at least 31 days after the last dose women of child bearing potential are not allowed to donate oocytes.

You may not qualify if:

• Part 1:
• Relevant diseases potentially interfering with the study objectives (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 ability to taste, as revealed by the taste-disturbance questionnaire during screening and the predose procedures
• Part 2:
• FEV1(Forced Expiratory Volume in 1 second) or FVC(Forced Vital Capacity ) 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 screening
• 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 (8)

Catharina Ziekenhuis

Eindhoven, North Brabant, 5623 EJ, Netherlands

Location

Isala

Zwolle, 8025 AB, Netherlands

Location

Queen's University

Belfast, Antrim, BT9 7BL, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, West Midlands, B9 5SS, 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

Medicines Evaluation Unit

Manchester, M23 9GP, United Kingdom

Location

University Hospital of South Manchester

Manchester, M23 9LT, United Kingdom

Location

Related Publications (1)

• Friedrich C, Francke K, Birring SS, van den Berg JWK, Marsden PA, McGarvey L, Turner AM, Wielders P, Gashaw I, Klein S, Morice AH. The P2X3 receptor antagonist filapixant in patients with refractory chronic cough: a randomized controlled trial. Respir Res. 2023 Apr 11;24(1):109. doi: 10.1186/s12931-023-02384-8.

  PMID: 37041539 DERIVED

Related Links

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

MeSH Terms

Conditions

Cough

Interventions

Midazolam

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

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

Model Details: Part 1: Sequential parallel-group Part 2: Two-arm crossover

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: May 24, 2018
• Study Start: May 29, 2018
• Primary Completion: September 25, 2019
• Study Completion: October 11, 2019
• Last Updated: February 10, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); GB (6)