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

Cough Clinical Trial

Official title:

Two-part, Double-blind, Placebo-controlled, Randomized, Parallel-group Study: (Part 1) in Healthy Male Subjects to Assess Safety and Tolerability of Ascending Repeated Oral Doses of BAY1902607 Including Its Effect on the Pharmacokinetics of a Sub-therapeutic Dose of Midazolam (MDZ), Followed by (Part 2) a Two-way Crossover Administration of Four Different Doses of BAY1902607 in Patients With Refractory Chronic Cough to Assess Safety, Tolerability and Efficacy for Proof of Concept

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03535168
• Other study ID #: 19430
• Secondary ID: 2018-000129-29
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 29, 2018
• Est. completion date: October 11, 2019

Study information

• Verified date: February 2021
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: October 11, 2019
• Est. primary completion date: September 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

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)

Related Conditions & MeSH terms

• Cough

Intervention

Drug:
• BAY1902607
3 different doses over the course of part 1 and 4 different doses over the course of part 2.
• Matching placebo
Matching placebo for BAY1902607
• Midazolam
Part 1: The subjects will initially (Day -1) receive a sub-therapeutic dose of 1 mg midazolam as solution in the morning.

Locations

Country	Name	City	State
Netherlands	Catharina Ziekenhuis	Eindhoven	Noord-Brabant
Netherlands	Isala	Zwolle
United Kingdom	Queen's University	Belfast	Antrim
United Kingdom	Birmingham Heartlands Hospital	Birmingham	West Midlands
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	King's College Hospital - NHS Foundation Trust	London
United Kingdom	Medicines Evaluation Unit	Manchester
United Kingdom	University Hospital of South Manchester	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 1		Approximately 5 weeks
Primary	Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 2		Approximately 12 weeks
Primary	AUC of midazolam without BAY1902607	Part 1	At Day -1
Primary	AUC of midazolam in combination with BAY1902607	Part 1	At Day 13
Primary	Cmax of midazolam in combination with BAY1902607	Part 1	At Day 13
Primary	Cmax of midazolam without BAY1902607	Part 1	At Day -1
Primary	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

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