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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT03310645

Collaborator

(none)

Enrollment

Locations

Arms

18.4

Actual Duration (Months)

12.4

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

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

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 patientsPart 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 :

Dec 7, 2017

Actual Primary Completion Date :

May 28, 2019

Actual Study Completion Date :

Jun 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 BAY
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 BAY
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 BAY

Outcome Measures

Primary Outcome Measures

Frequency of treatment emergent adverse events in study part 1 [Up to 5 weeks]
Severity of treatment emergent adverse events in study 1 [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
Frequency of treatment emergent adverse events in study part 2 [Up to 12 weeks]
Severity of treatment emergent adverse events in study part 2 [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
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Queen's University	Belfast	Antrim	United Kingdom	BT9 7BL
2	North Tyneside General Hospital	North Shields	Tyne And Wear	United Kingdom	NE29 8NH
3	Birmingham Heartlands Hospital	Birmingham	West Midlands	United Kingdom	B9 5SS
4	Castle Hill Hospital	Cottingham		United Kingdom	HU16 5JQ
5	King's College Hospital - NHS Foundation Trust	London		United Kingdom	SE5 9RS
6	University Hospital of South Manchester	Manchester		United Kingdom	M23 9LT
7	Medicines Evaluation Unit	Manchester		United Kingdom	M23 9QZ

Sponsors and Collaborators

Bayer

Investigators

Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Bayer

ClinicalTrials.gov Identifier:

NCT03310645

Other Study ID Numbers:

18184
2017-001620-22

First Posted:

Oct 16, 2017

Last Update Posted:

Jul 18, 2019

Last Verified:

Jul 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Bayer

Refractory chronic cough

healthy volunteers

Additional relevant MeSH terms:

Cough

Study Results

No Results Posted as of Jul 18, 2019