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

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03535168
• Collaborator: (none)
• Enrollment: 59
• Locations: 8
• Arms: 6
• Actual Duration (Months): 16.4
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cough	Drug: BAY1902607; Drug: Matching placebo; Drug: Midazolam	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Part 1: Sequential parallel-group Part 2: Two-arm crossoverPart 1: Sequential parallel-group Part 2: Two-arm crossover
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 29, 2018
• Actual Primary Completion Date: Sep 25, 2019
• Actual Study Completion Date: Oct 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose 1 of BAY1902607 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; 3 different doses over the course of part 1 and 4 different doses over the course of part 2.; Drug: Midazolam; Part 1: The subjects will initially (Day -1) receive a sub-therapeutic dose of 1 mg midazolam as solution in the morning.
Experimental: Dose 2 of BAY1902607 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; 3 different doses over the course of part 1 and 4 different doses over the course of part 2.; Drug: Midazolam; Part 1: The subjects will initially (Day -1) receive a sub-therapeutic dose of 1 mg midazolam as solution in the morning.
Experimental: Dose 3 of BAY1902607 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; 3 different doses over the course of part 1 and 4 different doses over the course of part 2.; Drug: Midazolam; Part 1: The subjects will initially (Day -1) receive a sub-therapeutic dose of 1 mg midazolam as solution in the morning.
Experimental: Matching placebo 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; Matching placebo for BAY1902607; Drug: Midazolam; Part 1: The subjects will initially (Day -1) receive a sub-therapeutic dose of 1 mg midazolam as solution in the morning.
Experimental: BAY1902607+Matching Placebo Part 2: Randomized crossover design in cough patients 4 different doses of BAY1902607+matching placebo	Drug: BAY1902607; 3 different doses over the course of part 1 and 4 different doses over the course of part 2.; Drug: Matching placebo; Matching placebo for BAY1902607
Experimental: Matching Placebo+BAY1902607 Part 2: Randomized crossover design in cough patients Matching placebo+4 different doses of BAY1902607	Drug: BAY1902607; 3 different doses over the course of part 1 and 4 different doses over the course of part 2.; Drug: Matching placebo; Matching placebo for BAY1902607

Outcome Measures

Primary Outcome Measures

1. Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 1 [Approximately 5 weeks]

2. Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 2 [Approximately 12 weeks]

3. AUC of midazolam without BAY1902607 [At Day -1]

   Part 1

4. AUC of midazolam in combination with BAY1902607 [At Day 13]

   Part 1

5. Cmax of midazolam in combination with BAY1902607 [At Day 13]

   Part 1

6. Cmax of midazolam without BAY1902607 [At Day -1]

   Part 1

7. Number of Coughs Experienced by the Patient Within a 24-hour Period (24- hour cough count/hour) in Part 2 [24 hours]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Catharina Ziekenhuis	Eindhoven	Noord-Brabant	Netherlands	5623 EJ
2	Isala	Zwolle		Netherlands	8025 AB
3	Queen's University	Belfast	Antrim	United Kingdom	BT9 7BL
4	Birmingham Heartlands Hospital	Birmingham	West Midlands	United Kingdom	B9 5SS
5	Castle Hill Hospital	Cottingham		United Kingdom	HU16 5JQ
6	King's College Hospital - NHS Foundation Trust	London		United Kingdom	SE5 9RS
7	Medicines Evaluation Unit	Manchester		United Kingdom	M23 9GP
8	University Hospital of South Manchester	Manchester		United Kingdom	M23 9LT

Sponsors and Collaborators

• Bayer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• 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

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03535168
• Other Study ID Numbers: 19430; 2018-000129-29
• First Posted: May 24, 2018
• Last Update Posted: Feb 10, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bayer: Healthy volunteers
• Additional relevant MeSH terms: Cough; Midazolam

Study Results

No Results Posted as of Feb 10, 2021