Idiopathic Pulmonary Fibrosis
Conditions
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.
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.
Interventions
DRUGGefapixant
Gefapixant oral tablet (150 mg administered as three 50 mg tablets) - single dose only
Sponsors
Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
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 1) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Gefapixant on BP | 6 hours | BP data will be summarized using descriptive statistics |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant 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 | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Gefapixant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| BP Mean Baseline Diastolic BP | 77 mmHg |
| BP Mean Baseline Systolic BP | 122 mmHg |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Effect of Gefapixant on BP
BP data will be summarized using descriptive statistics
Time frame: 6 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Gefapixant | Effect of Gefapixant on BP | Mean Systolic BP at 6 hrs | 122 units on a scale |
| Gefapixant | Effect of Gefapixant on BP | Mean Diastolic BP at 6 hrs | 76 units on a scale |