Asthma
Conditions
Brief summary
This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple dose treatment with MK-1029 in adults with mild to moderate persistent asthma.
Interventions
DRUGMK-1029
Five (5) X 100 mg capsules, orally, once daily for 28 days
DRUGPlacebo for MK-1029
Five (5) X 100 mg capsules, orally, once daily for 28 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* If female, must be of non-childbearing potential * Have a history of mild to moderate asthma for at least 6 months * Other than asthma, in general good health * Able to perform reproducible pulmonary function testing * Is a nonsmoker and/or has not used nicotine or nicotine-containing products for at least 12 months * Have body mass index (BMI) ≥17 kg/m\^2, but ≤35 kg/m\^2
Exclusion criteria
* Demonstrate a decrease in absolute forced expiratory volume in 1 second (FEV1) of \>20% from the Screening Visit to the Baseline Visit * Experience a decrease in AM or PM peak expiratory flow (PEF) below the Stability Limit on any 2 consecutive days prior to the Baseline Visit * Require the use of \>8 inhalations per day of short-acting beta2-agonist metered dose inhaler (MDI) or \>2 nebulized treatments per day of 2.5 mg albuterol, on any 2 consecutive days from the Screening Visit up to the Baseline Visit * Experience an exacerbation defined as a clinical deterioration of asthma, as judged by the clinical investigator, that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded medication (other than short-acting beta agonists \[SABA\]) at any time from the Screening Visit up to the Baseline Visit * Have been hospitalized for treatment of asthma or required oral corticosteroids for treatment of asthma within the past 6 months, or has ever required ventilator support for respiratory failure secondary to asthma * Require the chronic use of high-dose inhaled corticosteroids * Have been diagnosed with chronic obstructive pulmonary disease (COPD) or any other clinically relevant lung disease, other than asthma * Have a history of any illness that might confound the results of the study or poses additional risk to the participant * Have had recent (within 4 weeks of first dose) or ongoing upper or lower respiratory tract infection * Is nursing * Have a history of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced One or More Adverse Events | Up to 42 days after initial dose of study treatment | An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Number of Participants Who Discontinued Study Treatment Due to An Adverse Event | Up to 28 days after initial dose of study treatment | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 to 6 Hours (AUC0-6hr) of MK-1029 | Day 1 and Day 28: Predose, 1, 2, 3, 4, and 6 hours postdose | Blood was collected on Day 1 and Day 28 at predose and 1, 2, 3, 4 and 6 hours postdose for determining the Cmax of MK-1026. |
| Maximum Plasma Concentration (Cmax) of MK-1029 | Day 1 and Day 28: Predose, 1, 2, 3, 4, and 6 hours postdose | Blood was collected on Day 1 and Day 28 at predose and 1, 2, 3, 4 and 6 hours postdose for determining the Cmax of MK-1026. |
| Time to Maximum Plasma Concentration (Tmax) of MK-1029 | Day 1 and Day 28: Predose, 1, 2, 3, 4, and 6 hours postdose | Blood was collected on Day 1 and Day 28 at predose and 1, 2, 3, 4 and 6 hours postdose for determining the Tmax of MK-1026. |
Countries
Australia, New Zealand, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-1029 Participants received five 100 mg MK-1029 capsules, taken orally, once daily for 28 days. | 18 |
| Placebo Participants received five 100 mg placebo-matching MK-1029 capsules, taken orally, once daily for 28 days. | 9 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Participant withdrew consent | 1 | 0 |
| Overall Study | Protocol deviation | 0 | 1 |
Baseline characteristics
| Characteristic | MK-1029 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 40.4 Years STANDARD_DEVIATION 15.2 | 41.6 Years STANDARD_DEVIATION 13.5 | 40.8 Years STANDARD_DEVIATION 14.4 |
| Sex: Female, Male Female | 9 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 9 |
| other Total, other adverse events | 9 / 18 | 3 / 9 |
| serious Total, serious adverse events | 0 / 18 | 0 / 9 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to An Adverse Event
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 28 days after initial dose of study treatment
Population: All participants who received at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-1029 | Number of Participants Who Discontinued Study Treatment Due to An Adverse Event | 0 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment Due to An Adverse Event | 0 Participants |
Primary
Number of Participants Who Experienced One or More Adverse Events
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 42 days after initial dose of study treatment
Population: All participants who received at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-1029 | Number of Participants Who Experienced One or More Adverse Events | 9 Participants |
| Placebo | Number of Participants Who Experienced One or More Adverse Events | 3 Participants |
Secondary
Area Under the Concentration-Time Curve From Time 0 to 6 Hours (AUC0-6hr) of MK-1029
Blood was collected on Day 1 and Day 28 at predose and 1, 2, 3, 4 and 6 hours postdose for determining the Cmax of MK-1026.
Time frame: Day 1 and Day 28: Predose, 1, 2, 3, 4, and 6 hours postdose
Population: All participants who received study drug and had evaluable concentration values for AUC0-6 hours on Day 1 and Day 28
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-1029 | Area Under the Concentration-Time Curve From Time 0 to 6 Hours (AUC0-6hr) of MK-1029 | Day 1 | 745 ng*hr/mL | Geometric Coefficient of Variation 104 |
| MK-1029 | Area Under the Concentration-Time Curve From Time 0 to 6 Hours (AUC0-6hr) of MK-1029 | Day 28 | 505 ng*hr/mL | Geometric Coefficient of Variation 275 |
Secondary
Maximum Plasma Concentration (Cmax) of MK-1029
Blood was collected on Day 1 and Day 28 at predose and 1, 2, 3, 4 and 6 hours postdose for determining the Cmax of MK-1026.
Time frame: Day 1 and Day 28: Predose, 1, 2, 3, 4, and 6 hours postdose
Population: All participants who received study drug and had evaluable concentration values for Cmax on Day 1 and Day 28
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-1029 | Maximum Plasma Concentration (Cmax) of MK-1029 | Day 1 | 295 ng/mL | Geometric Coefficient of Variation 106 |
| MK-1029 | Maximum Plasma Concentration (Cmax) of MK-1029 | Day 28 | 167 ng/mL | Geometric Coefficient of Variation 273 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of MK-1029
Blood was collected on Day 1 and Day 28 at predose and 1, 2, 3, 4 and 6 hours postdose for determining the Tmax of MK-1026.
Time frame: Day 1 and Day 28: Predose, 1, 2, 3, 4, and 6 hours postdose
Population: All participants who received study drug and had evaluable concentration values for Tmax on Day 1 and Day 28
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MK-1029 | Time to Maximum Plasma Concentration (Tmax) of MK-1029 | Day 1 | 2.00 Hours |
| MK-1029 | Time to Maximum Plasma Concentration (Tmax) of MK-1029 | Day 28 | 3.00 Hours |