Chronic Cough
Conditions
Keywords
refractory cough, cough hypersensitivity, ADX-629, unexplained cough, reactive aldehyde species, crossover, inflammation
Brief summary
A Randomized, Double-Blind, Placebo-Controlled, Two-Period Crossover, Phase 2 Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of ADX-629 Administered Orally to Subjects with Chronic Cough
Detailed description
A Phase 2, multicenter, randomized, double-blind, placebo controlled, two-period crossover trial to evaluate the safety, tolerability, and efficacy of ADX-629 (300 mg) administered orally, twice-a-day to eligible participants with refractory or unexplained chronic cough. Patients who are interested in participating will be provided detailed information about the study including description of study assessments/procedures, possible side-effects, alternative treatments, and potential benefits.
Interventions
DRUGADX-629
Subjects will be randomized to receive both ADX-629 and placebo in one of two treatment sequences: One group of subjects will receive ADX-629 during the 1st treatment period and matching placebo during the 2nd Treatment while subjects the other sequence/group will receive the matching placebo in the 1st treatment period and ADX-629 in the 2nd treatment period.
DRUGPlacebo
Subjects will be randomized to receive both ADX-629 and placebo in one of two treatment sequences: One group of subjects will receive ADX-629 during the 1st treatment period and matching placebo during the 2nd Treatment while subjects the other sequence/group will receive the matching placebo in the 1st treatment period and ADX-629 in the 2nd treatment period.
Sponsors
Aldeyra Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adults ≥18 to ≤80 years of age * History of refractory or unexplained chronic cough * Historical Chest radiograph or CT scan that does not demonstrate any abnormality considered to be significantly contributing to chronic cough * Not pregnant, breastfeeding, or lactating and agree to use a highly effective method of acceptable contraceptive for the trial duration, if applicable * Agree to discontinue antitussive medications for the trial duration
Exclusion criteria
* Current smoker (including cannabis products) or previous smoker having recently given up smoking or has a history of smoking of \>20 pack-years * History of significant cardiovascular disease or any clinically significant abnormalities in rhythm or conduction * History or presence of significant hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. * History of any malignancy within 5 years of screening except for basal cell or squamous cell in situ skin carcinomas or carcinoma in situ of the cervix that has been treated with no evidence of recurrence. * Recent history of drug or alcohol abuse or a positive urine drug test at screening * Positive serology test for Hepatitis B virus (HBV), Hepatitis C virus (HCV), or HIV-1 and HIV-2 * Currently taking an angiotensin converting enzyme inhibitor (ACEI) or has used an ACEI within 3 months of Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Serious Adverse Events | The safety assessment period was Day 1 - Day 14 for each treatment period. | Safety was assessed through serious adverse event collection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Awake Cough Frequency Per Hour With Prior Treatment as a Factor | The efficacy assessment period was Day 14 for each treatment period. Baseline was Day 1 prior to dosing for each treatment period. | Change from baseline in cough count was assessed while subjects were awake using a cough monitor with a digital recording device. The number of coughs is proportional to disease severity. Estimates were obtained using mixed model repeated measures (MMRM) analysis with treatment and prior treatment (none for Period 1; Period 1 treatment for Period 2) as fixed effects, and period-specific baseline as a covariate. |
| Change From Baseline in 24-hour Cough Frequency Per Hour With Prior Treatment as a Factor | The efficacy assessment period was Day 14 for each treatment period. Baseline was Day 1 prior to dosing for each treatment period. | Change from baseline in cough count was assessed for twenty-four hours using a cough monitor with a digital recording device. Number of coughs is associated with disease severity. Estimates were obtained using MMRM analysis with treatment and prior treatment (none for Period 1; Period 1 treatment for Period 2) as fixed effects, and period-specific baseline as a covariate. |
| Change From Baseline in Awake Cough Frequency Per Hour for Period 1 | The efficacy assessment period was Day 14. Baseline was Day 1 for Period 1. | Change from baseline in cough count in Period 1 was assessed while subjects were awake using a cough monitor with a digital recording device. The number of coughs is proportional to disease severity. Estimates were obtained using MMRM analysis with treatment as fixed effect, and Period 1-specific baseline as a covariate. |
| Change From Baseline in 24-hour Cough Frequency Per Hour for Period 1 | The efficacy assessment period was Day 14. Baseline was Day 1 for Period 1. | Change from baseline in cough count in Period 1 was assessed for twenty-four hours using a cough monitor with a digital recording device. The number of coughs is proportional to disease severity. Estimates were obtained using MMRM analysis with treatment as fixed effect, and Period 1-specific baseline as a covariate. |
Countries
United States
Participant flow
Pre-assignment details
Fifty-one subjects were randomized in a crossover design.
Participants by arm
| Arm | Count |
|---|---|
| ADX-629 First, Then Placebo ADX-629 300mg administered orally BID for two weeks, followed by a two-week washout, then placebo administered orally BID for two weeks. | 26 |
| Placebo First, Then ADX-629 Placebo administered orally BID for two weeks, followed by a two-week washout, then ADX-629 300mg administered orally BID for two weeks. | 25 |
| Total | 51 |
Baseline characteristics
| Characteristic | Total | ADX-629 First, Then Placebo | Placebo First, Then ADX-629 |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 8.3 | 65.3 years STANDARD_DEVIATION 9.5 | 65.2 years STANDARD_DEVIATION 7.1 |
| Body Mass Index | 28.9 kg/m2 STANDARD_DEVIATION 7.4 | 29.4 kg/m2 STANDARD_DEVIATION 9.5 | 28.4 kg/m2 STANDARD_DEVIATION 4.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 25 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 47 Participants | 23 Participants | 24 Participants |
| Sex: Female, Male Female | 42 Participants | 21 Participants | 21 Participants |
| Sex: Female, Male Male | 9 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 51 |
| other Total, other adverse events | 3 / 51 | 0 / 51 |
| serious Total, serious adverse events | 0 / 51 | 0 / 51 |
Outcome results
Primary
Number of Subjects With Serious Adverse Events
Safety was assessed through serious adverse event collection.
Time frame: The safety assessment period was Day 1 - Day 14 for each treatment period.
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADX-629 | Number of Subjects With Serious Adverse Events | 0 Participants |
| Placebo | Number of Subjects With Serious Adverse Events | 0 Participants |
Secondary
Change From Baseline in 24-hour Cough Frequency Per Hour for Period 1
Change from baseline in cough count in Period 1 was assessed for twenty-four hours using a cough monitor with a digital recording device. The number of coughs is proportional to disease severity. Estimates were obtained using MMRM analysis with treatment as fixed effect, and Period 1-specific baseline as a covariate.
Time frame: The efficacy assessment period was Day 14. Baseline was Day 1 for Period 1.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ADX-629 | Change From Baseline in 24-hour Cough Frequency Per Hour for Period 1 | -9.39 coughs per hour |
| Placebo | Change From Baseline in 24-hour Cough Frequency Per Hour for Period 1 | 2.02 coughs per hour |
Secondary
Change From Baseline in 24-hour Cough Frequency Per Hour With Prior Treatment as a Factor
Change from baseline in cough count was assessed for twenty-four hours using a cough monitor with a digital recording device. Number of coughs is associated with disease severity. Estimates were obtained using MMRM analysis with treatment and prior treatment (none for Period 1; Period 1 treatment for Period 2) as fixed effects, and period-specific baseline as a covariate.
Time frame: The efficacy assessment period was Day 14 for each treatment period. Baseline was Day 1 prior to dosing for each treatment period.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ADX-629 | Change From Baseline in 24-hour Cough Frequency Per Hour With Prior Treatment as a Factor | -5.57 coughs per hour |
| Placebo | Change From Baseline in 24-hour Cough Frequency Per Hour With Prior Treatment as a Factor | 6.39 coughs per hour |
Secondary
Change From Baseline in Awake Cough Frequency Per Hour for Period 1
Change from baseline in cough count in Period 1 was assessed while subjects were awake using a cough monitor with a digital recording device. The number of coughs is proportional to disease severity. Estimates were obtained using MMRM analysis with treatment as fixed effect, and Period 1-specific baseline as a covariate.
Time frame: The efficacy assessment period was Day 14. Baseline was Day 1 for Period 1.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ADX-629 | Change From Baseline in Awake Cough Frequency Per Hour for Period 1 | -11.51 coughs per hour |
| Placebo | Change From Baseline in Awake Cough Frequency Per Hour for Period 1 | 2.45 coughs per hour |
Secondary
Change From Baseline in Awake Cough Frequency Per Hour With Prior Treatment as a Factor
Change from baseline in cough count was assessed while subjects were awake using a cough monitor with a digital recording device. The number of coughs is proportional to disease severity. Estimates were obtained using mixed model repeated measures (MMRM) analysis with treatment and prior treatment (none for Period 1; Period 1 treatment for Period 2) as fixed effects, and period-specific baseline as a covariate.
Time frame: The efficacy assessment period was Day 14 for each treatment period. Baseline was Day 1 prior to dosing for each treatment period.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ADX-629 | Change From Baseline in Awake Cough Frequency Per Hour With Prior Treatment as a Factor | -7.06 coughs per hour |
| Placebo | Change From Baseline in Awake Cough Frequency Per Hour With Prior Treatment as a Factor | 7.68 coughs per hour |