A Study to Assess the Tolerability of a Single Dose of Gefapixant (AF-219/MK-7264) in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

• Sponsor: Afferent Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02477709
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 1.1
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

This study assesses the tolerability of a single dose of gefapixant (AF-219) in participants with idiopathic pulmonary fibrosis (IPF). Six eligible participants will receive a single 150 mg dose of gefapixant and undergo tolerability and PK assessments.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Gefapixant	Phase 2

Detailed Description

This study assesses the tolerability of a single dose of gefapixant in participants with idiopathic pulmonary fibrosis (IPF).

This will be the first experience of administering gefapixant in patients with IPF. P2X3 receptors are found on the chemosensory afferents of the carotid body and can influence sympathetic autonomic discharge, especially in sensitized subjects; accordingly, by blocking these P2X3 receptors, gefapixant may have an effect of reducing sympathetic activity. Therefore in order to determine whether P2X3 antagonism would have an effect on the hemodynamic measures such as blood pressure in patients with IPF, study AF219-019 is being performed. These patients will be closely monitored in order to determine any such effect.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Assess the Tolerability of a Single Dose of AF-219, a P2X3 Receptor Antagonist, in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
• Actual Study Start Date: Jul 20, 2015
• Actual Primary Completion Date: Aug 7, 2015
• Actual Study Completion Date: Aug 21, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gefapixant Gefapixant oral tablets (150 mg) administered as a single dose	Drug: Gefapixant; Gefapixant oral tablet (150 mg administered as three 50 mg tablets) - single dose only; Other Names: AF-219 MK-7264

Outcome Measures

Primary Outcome Measures

1. Effect of Gefapixant on BP [6 hours]

   BP data will be summarized using descriptive statistics

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Idiopathic pulmonary fibrosis diagnosis based upon the American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) IPF 2011 guideline

• Life expectancy of greater than 6 months

• Stable medical condition (IPF) for at least 4 weeks

• Women of child-bearing potential must use 2 forms of an acceptable birth control method from Screening through the Follow-Up Visit

• Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control, 1 of which must be a barrier method, and make no donation of sperm from Screening until 3 months after the last dose of study drug

• Written informed consent

• Willing and able to comply with all aspects of the protocol

Exclusion Criteria:

• Current smoker (i.e., within the last 30 days)

• Initiation of treatment with an antihypertensive agent within 4 weeks prior to the day of dosing (Day 1) or during the study

• History of upper respiratory tract infection within 4 weeks of the day of dosing (Day

• Requiring concomitant therapy with prohibited medications

• Body mass index (BMI) <18 kg/m2 or ≥ 40 kg/m2

• History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas)

• History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years

• Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, fundoplication, any type of bariatric surgery, vagotomy, or bowel resection)

• Recent history of stroke or transient ischemic attack (within 6 months prior to Screening) not due to trauma, repaired vascular malformation, or aneurysm

• Screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure (DBP)

90 mm Hg

• QTc interval >450 milliseconds in males, >470 milliseconds in females

• Breastfeeding

• Treatment with an investigational drug or biologic within 30 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion

• Blood donation within 56 days or plasma donation within 7 days prior to dosing

• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	American Health Research	Charlotte	North Carolina	United States	28207

Sponsors and Collaborators

• Afferent Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Selwyn Spangenthal, American Health Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Afferent Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02477709
• Other Study ID Numbers: 7264-019; AF219-019
• First Posted: Jun 23, 2015
• Last Update Posted: Jun 25, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis

Study Results

Participant Flow

Arm/Group Title	Gefapixant
Arm/Group Description	Gefapixant oral tablets (150 mg) administered as a single dose gefapixant: gefapixant oral tablet (150 mg administered as three 50 mg tablets) - single dose only
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gefapixant
Arm/Group Description	Gefapixant oral tablets (150 mg) administered as a single dose gefapixant: gefapixant oral tablet (150 mg administered as three 50 mg tablets) - single dose only
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 33.3%
>=65 years	4 66.7%
Sex: Female, Male (Count of Participants)
Female	2 33.3%
Male	4 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%
Not Hispanic or Latino	5 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 33.3%
White	4 66.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%
BP (mmHg) [Mean (Full Range) ]
Mean Baseline Systolic BP	122
Mean Baseline Diastolic BP	77

Outcome Measures

1. Primary Outcome

Title	Effect of Gefapixant on BP
Description	BP data will be summarized using descriptive statistics
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gefapixant
Arm/Group Description	Gefapixant oral tablets (150 mg) administered as a single dose gefapixant: gefapixant oral tablet (150 mg administered as three 50 mg tablets) - single dose only
Measure Participants	6
Mean Systolic BP at 6 hrs	122
Mean Diastolic BP at 6 hrs	76

Adverse Events

Time Frame	2 weeks
Arm/Group Title	Gefapixant
Arm/Group Description	Gefapixant oral tablets (150 mg) administered as a single dose gefapixant: gefapixant oral tablet (150 mg administered as three 50 mg tablets) - single dose only
All Cause Mortality
	Gefapixant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gefapixant
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Gefapixant
	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)
Eye disorders
Vision Blurred	1/6 (16.7%)	1
General disorders
Pain	1/6 (16.7%)	1
Feeling Hot	1/6 (16.7%)	1
Local Swelling	1/6 (16.7%)	2
Asthenia	1/6 (16.7%)	1
Metabolism and nutrition disorders
Decreased Appetite	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/6 (16.7%)	1
Nervous system disorders
Hypogeusia	3/6 (50%)	4
Dysgeusia	2/6 (33.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

60 days prior to the submission of any results, the PI shall submit to SPONSOR any proposed PUBLICATION, which period may be extended for an additional 30 days if requested by SPONSOR. If any Confidential Information should be redacted or patent applications relating to an Invention should be filed prior to PUBLICATION, then PUBLICATION will be delayed until patent application has been filed. Delay of a PUBLICATION shall not exceed 24 months from the date of such notice to the PI.