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MK-1029

Phase 2

Asthma | Small molecule | Respiratory |Merck & Company, Inc.|Last Updated: Mar 1, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials4
Total Enrollment292
FDA Designations
No designations recorded
Clinical Trials (4)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02720081Study of MK-1029 in Participants With Persistent Asthma That Cannot Be Controlled With Montelukast (MK-1029-015)PHASE2 COMPLETED 142May 11, 2016Sep 6, 2017Sep 27, 2018 -
NCT01624974Study to Evaluate the Effectiveness and Safety of MK-1029 in the Treatment of Persistent Asthma That is Not Controlled With Montelukast (ML) in Adults (MK-1029-011)PHASE2 COMPLETED 107Aug 9, 2012May 5, 2014Jan 2, 2019 -
NCT01370317Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1029 in Participants With Mild to Moderate AsthmaPHASE1 COMPLETED 27Jun 1, 2011Dec 27, 2011Jan 25, 20195 United States, Australia +2
NCT01343407A Two-part Study of the Effects of MK-1029 in Allergen-Challenged Asthmatics (MK-1029-003)PHASE1 COMPLETED 16Apr 19, 2011Jan 9, 2012Mar 1, 2019 -
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Study Endpoints
Primary Endpoints
Baseline Pre-dose Forced Expiratory Volume in One Second (FEV1)
Before the first dose of study investigational product (Baseline)

FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second.

Average Change From Baseline in Pre-dose FEV1 at Week 4 and Week 6
Before the first dose (Baseline) and at the end of Weeks 4 and 6 of treatment

FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. Data presented represents the average change from baseline at Week 4 and Week 6.

Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 4
The week before the first dose in Period III or V (Baseline) and the last week of Period III or V

The change from baseline in FEV1 at Week 4 following treatment with MK-1029 + ML or placebo + ML was assessed. The pre-bronchodilator FEV1 was evaluated to assess the response to treatment for asthma. The primary efficacy evaluation period was the last week of each treatment period: Period III (Initial Therapy, Week 4) and Period V (Crossover Therapy, Week 4). The change from baseline in FEV1 was evaluated using a longitudinal data analysis (LDA) model with repeated measurements of FEV1, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect. Baseline FEV1 is defined as the measurement taken before dosing in each treatment period (i. e., at Visit 3 \[Week 0\], prior to Period III and at Visit 6 \[Week 8\], prior to Period V). The Baseline Characteristics section shows FEV1 values at baseline.

Adverse Events During Treatment and Follow-up
Up to 14 days after the last dose in Period III or Period V (up to 6 weeks)

The number of participants who had at least one adverse event (AE) during study treatment and follow-up was assessed. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. The number of participants with at least one AE was assessed. The number of participants in any treatment group with at least one AE was assessed.

Discontinuation of Treatment Due to An Adverse Event
Up to the last dose in Period III or Period V (up to 4 weeks)

The number of participants who discontinued study treatment due to an AE was assessed. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.

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.

Percent Change From Baseline in Percent (%) Eosinophils in Induced Sputum At 8 Hours Post Allergen
Baseline (Day -1) and Day 5 (8 hours after allergen challenge in each treatment period)

The effect of MK-1029 on the reduction of percent (%) sputum eosinophils following allergen challenge with standardized cat pelt or hair (CPH) allergen extract was assessed. Baseline % eosinophils were measured before treatment (and pre-allergen challenge) on Day -1. The change from baseline in allergen-induced % sputum eosinophils at 8 hr post allergen challenge testing on Day 5 was analyzed using a repeated measures linear mixed effects model with treatment, period, time, time-by-treatment interaction as fixed factors, and participant as a random factor. Outcome Measure 6 shows % eosinophil values at baseline.

Forced Expiratory Volume in One Second (FEV1) From 3 to 8 Hours Postdose (AUC3-8hr) During the Late Asthmatic Response (LAR)
From 3 to 8 hours after allergen challenge on Day 5 of each treatment period

The effect of MK-1029 on the FEV1 AUC(3-8hr) during LAR was assessed. The unit of measure for an FEV1 AUC value is L\*hr. The effect of treatment on LAR was assessed as the percent-fall in FEV1 AUC(3-8hr), evaluated by spirometry following allergen challenge on Day 5. The FEV1 AUC(3-8hr) during LAR was analyzed using a linear mixed effects model with treatment and period as fixed factors and participant as a random factor.

Number of Participants With an Adverse Event (AE)
Up to 26 days in each treatment period

The number of participants who had at least one adverse event (AE) during study treatment and follow-up was assessed. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.

Number of Participants Discontinuing Treatment Due to an AE
Up to 5 days in each treatment period

The number of participants who discontinued study treatment due to an AE was assessed. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.

Secondary Endpoints
Percentage of Days With Worsening Asthma Average Over Weeks 3 to 6
Up to 4 weeks
Percentage of Participants Who Experienced an Adverse Event (AE)
Up to 8 weeks
Percentage of Participants Who Discontinued Study Drug Due to an AE
Up to 6 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
MK-1029 150 mg + Montelukast 10 mgEXPERIMENTALParticipants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 150 mg + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed.
MK-1029 Placebo + Montelukast 10 mgPLACEBO_COMPARATORParticipants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 Matching-image Placebo + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed.
MK-1029/PlaceboEXPERIMENTALParticipants received 4 weeks treatment with MK-1029 150 mg once daily (QD) + ML 10 mg QD in Period III and Placebo QD + ML 10 mg QD in Period V. Period IV was a 4-week wash-out period during which participants received single-blind Placebo QD and open-label ML 10 mg QD.
Placebo/MK-1029EXPERIMENTALParticipants received 4 weeks treatment with Placebo QD + ML 10 mg QD in Period III and MK-1029 150 mg QD + ML 10 mg QD in Period V. Period IV was a 4-week wash-out period during which participants received single-blind Placebo QD and open-label ML 10 mg QD.
MK-1029EXPERIMENTAL -
PlaceboPLACEBO_COMPARATOR -
MK-1029 60 mgEXPERIMENTALPart 2 - Participants will receive 5 days of double-blind, once-daily MK-1029 60 mg followed by a 21-day washout in Period 2, 3, or 4 in a crossover design
MK-1029 500 mgEXPERIMENTALPart 2 - Participants will receive 5 days of double-blind, once-daily MK-1029 60 mg followed by a 21-day washout in Period 2, 3, or 4 in a crossover design
Interventions
NameTypeDescription
MK-1029 150 mgDRUG150 mg tablet administered orally, once a day (QD), at bedtime
MK-1029 Matching-image PlaceboDRUGMatching-image placebo tablet administered orally, QD, at bedtime
Montelukast 10 mgDRUG10 mg tablet administered orally, QD, at bedtime
Albuterol/Salbutamol 90 mcg - 100 mcg per inhalationDRUG1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication
MK-1029DRUGMK-1029 150 mg tablets taken QD
PlaceboDRUGPlacebo tablets (matching the MK-1029 150 mg tablets) QD
Montelukast (ML)DRUGML 10 mg tablets QD
Placebo for MK-1029DRUGFive (5) X 100 mg capsules, orally, once daily for 28 days
MK-1029 10 mgDRUGSix capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design
MK-1029 100 mgDRUGFive capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design
Placebo for MK-1029 10 mgDRUGSix capsules once daily for 5 days in Period 1, and the same in Period 2, 3, or 4 in a crossover design."
Placebo for MK-1029 100 mgDRUGFive capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design
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Eligibility Criteria
Age Range18 Years — 65 Years
SexALL
Healthy VolunteersNo

Inclusion Criteria: * Symptoms of persistent asthma for at least one year * History of asthma treatments including "as-needed" inhaled short-acting beta-agonists (albuterol/salbutamol); stable doses of inhaled corticosteroids (ICS), combination ICS/long-acting (inhaled) Beta2-adrenergic agonist (LA...

Countries:United StatesAustraliaNew ZealandSouth Africa
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