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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-022391-31 | EudraCT Number | ||
| MK-1029-003 | Other Identifier | Merck Protocol Number |
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This was a 2-part study in participants with allergen-induced asthma. It included a procedural pilot component (Part 1). Part 1 tested the key procedures and timing of Part 2; no study drug was administered during Part 1. Part 2 included a pre-randomization placebo run-in (Period 1) and 3 treatment periods (Periods 2, 3, and 4) during which participants were randomized to receive double-blind placebo, MK-1029 60 mg or MK-1029 500 mg in a crossover design. The treatment periods were followed by a minimum 21-day washout. Part 2 assessed allergen-induced sputum eosinophils and allergen-induced late asthmatic response (LAR) compared to placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-1029 60 mg | Experimental | Part 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 mg | Experimental | Part 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 |
|
| Placebo | Placebo Comparator | Part II - 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-1029 10 mg | Drug | Six capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Percent (%) Eosinophils in Induced Sputum At 8 Hours Post Allergen | 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. | Baseline (Day -1) and Day 5 (8 hours after allergen challenge in each treatment period) |
| Forced Expiratory Volume in One Second (FEV1) From 3 to 8 Hours Postdose (AUC3-8hr) During the Late Asthmatic Response (LAR) | 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. | From 3 to 8 hours after allergen challenge on Day 5 of each treatment period |
| Number of Participants With an Adverse Event (AE) | 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. | Up to 26 days in each treatment period |
| Number of Participants Discontinuing Treatment Due to an AE | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Inhibition of the Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils | The concentration of CD11b in whole blood samples was assessed. The percent-inhibition of CD11b (a cell-surface biomarker on activated eosinophils) was assessed following inhaled allergen challenge on Day 5. Inhibition of CD11b expression was assessed by analyzing the % inhibition of CD11b expression from baseline (Day -1) using a linear mixed-effects model with period, treatment, time, and treatment by time as fixed terms and subject as a random term. Outcome Measure 7 shows CD11b expression values at baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline (Pre-Treatment) Percent (%) Eosinophils | Baseline values of the percent (%) sputum eosinophils were measured pre-antigen challenge on Day -1. The baseline % eosinophil values were provided to assess the change from baseline after treatment. | Baseline (Day -1), pre-antigen challenge |
| Baseline Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils |
Inclusion Criteria:
Parts 1 and 2
Part 2 only
Exclusion Criteria:
Parts 1 and 2
other potential asthma/anaphylaxis rescue medication
Part 2 only
- Has a decline in FEV1 of 70% or greater from the post allergen diluent baseline and/or FEV1 <1.0L or has symptomatic drop in FEV1 associated with shortness of breath unresolved with bronchodilators within a reasonable timeframe (60 minutes) after the allergen challenge study in Period 1
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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This was a 2-part study. Part 1 was a procedural pilot, performed first and including placebo run-in (Period 1), with no study drug administration. Part 2 began with pre-randomization placebo run-in (Period 1), followed by 3 randomized, crossover treatment periods (Periods 2, 3, and 4). The Participant Flow applies only to randomized participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | Placebo→MK-1029 60 mg→ MK-1029 500 mg. Participants received 5 days of crossover treatment (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods. |
| FG001 | Sequence 2 | MK-1029 60 mg→MK-1029 500 mg→Placebo. Participants received 5 days of crossover treatment (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods. |
| FG002 | Sequence 3 | MK-1029 500 mg→Placebo→ MK-1029 60 mg. Participants received 5 days of crossover treatment (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods. |
| FG003 | Sequence 4 | Placebo→MK-1029 500 mg→ MK-1029 60 mg. Participants received 5 days of crossover treatment (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods. |
| FG004 | Sequence 5 | MK-1029 500 mg→MK-1029 60 mg→Placebo. Participants received 5 days of crossover treatment (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods. |
| FG005 | Sequence 6 | MK-1029 60 mg→Placebo→ MK-1029 500 mg. Participants received 5 days of crossover treatment (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Treatment Period (Part 2) |
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| First Washout (Part 2) |
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| Second Treatment Period (Part 2) |
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| Second Washout (Part 2) |
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| Third Treatment Period (Part 2) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Randomized Participants | Crossover treatment with MK-1029 60 mg, MK-1029 500 mg, and matching placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Percent (%) Eosinophils in Induced Sputum At 8 Hours Post Allergen | 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. | Participants who comply with the protocol sufficiently to ensure data obtained will be likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Least Squares Mean | 95% Confidence Interval | Percent change | Baseline (Day -1) and Day 5 (8 hours after allergen challenge in each treatment period) |
|
Up to 26 days in each treatment period
One participant had an episode of respiratory distress (a serious AE) during the placebo run-in, and was not randomized to study treatment. The at-risk population for AEs is all participants who received study drug in a treatment period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 60 mg MK-1029 | Participants received 5 days of treatment with MK-1029 60 mg (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gingival pain | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| MK-1029 100 mg | Drug | Five capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design |
|
| Placebo for MK-1029 10 mg | Drug | Six 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 mg | Drug | Five capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design |
|
| Up to 5 days in each treatment period |
| Baseline (Day -1, predose), 24 hours after allergen challenge on Day 5 in each treatment period |
Baseline values for the antibody-specific expression of CD11b in whole blood samples, as obtained by flow cytometry, were obtained. The baseline CD11b values were obtained before treatment with MK-1029 60 mg, MK-1029 500 mg, or placebo, and were used to assess the effects of treatment. |
| Day 1, predose |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 |
| MK-1029 60 mg |
Participants received 5 days of treatment with MK-1029 60 mg (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods |
| OG001 | MK-1029 500 mg | Participants received 5 days of treatment with MK-1029 500 mg (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods |
| OG002 | Placebo | Participants received 5 days of treatment with placebo (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods |
|
|
|
| Primary | Forced Expiratory Volume in One Second (FEV1) From 3 to 8 Hours Postdose (AUC3-8hr) During the Late Asthmatic Response (LAR) | 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. | Participants who comply with the protocol sufficiently to ensure data obtained will be likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Least Squares Mean | 95% Confidence Interval | L*hr | From 3 to 8 hours after allergen challenge on Day 5 of each treatment period |
|
|
|
|
| Secondary | Percent Inhibition of the Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils | The concentration of CD11b in whole blood samples was assessed. The percent-inhibition of CD11b (a cell-surface biomarker on activated eosinophils) was assessed following inhaled allergen challenge on Day 5. Inhibition of CD11b expression was assessed by analyzing the % inhibition of CD11b expression from baseline (Day -1) using a linear mixed-effects model with period, treatment, time, and treatment by time as fixed terms and subject as a random term. Outcome Measure 7 shows CD11b expression values at baseline. | Participants who comply with the protocol sufficiently to ensure data obtained will be likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Least Squares Mean | 95% Confidence Interval | Percentage of inhibition | Baseline (Day -1, predose), 24 hours after allergen challenge on Day 5 in each treatment period |
|
|
|
|
| Primary | Number of Participants With an Adverse Event (AE) | 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. | All randomized participants who received at least one dose of study treatment and had follow-up. | Posted | Count of Participants | Participants | Up to 26 days in each treatment period |
|
|
|
| Primary | Number of Participants Discontinuing Treatment Due to an AE | 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. | All randomized participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to 5 days in each treatment period |
|
|
|
| Other Pre-specified | Baseline (Pre-Treatment) Percent (%) Eosinophils | Baseline values of the percent (%) sputum eosinophils were measured pre-antigen challenge on Day -1. The baseline % eosinophil values were provided to assess the change from baseline after treatment. | Participants who were compliant with the protocol sufficiently to ensure their data would be likely to exhibit the effects of treatment were included. | Posted | Mean | Full Range | % sputum eosinophils | Baseline (Day -1), pre-antigen challenge |
|
|
|
| Other Pre-specified | Baseline Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils | Baseline values for the antibody-specific expression of CD11b in whole blood samples, as obtained by flow cytometry, were obtained. The baseline CD11b values were obtained before treatment with MK-1029 60 mg, MK-1029 500 mg, or placebo, and were used to assess the effects of treatment. | Participants who were compliant with the protocol sufficiently to ensure their data would be likely to exhibit the effects of treatment were included. | Posted | Mean | Standard Deviation | Antibody fluorescence units | Day 1, predose |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 11 |
| 14 |
| EG001 | 500 mg MK-1029 | Participants received 5 days of treatment with MK-1029 500 mg (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods | 0 | 16 | 0 | 16 | 10 | 16 |
| EG002 | Placebo | Participants received 5 days of treatment with placebo (once-daily dosing) in 3 periods, followed by a minimum 21-day washout between treatment periods | 0 | 16 | 0 | 16 | 11 | 16 |
| Catheter site erythema | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 14.1 | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA 14.1 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 14.1 | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 14.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Breast mass | Reproductive system and breast disorders | MedDRA 14.1 | Systematic Assessment |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Systematic Assessment |
|
This study is intended for publication, even if terminated prematurely. The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Linear mixed effects model |
| 0.012 |
| LS Mean Ratio (LSMR) |
| 0.58 |
| 2-Sided |
| 90 |
| 0.41 |
| 0.81 |
| Other |
% Inhibition: 42.4 (90% CI: 19.3, 58.8) The % Inhibition of FEV1*hr (reduction of the allergen-induced LAR) for MK-1029 vs Placebo was calculated as 100*(1-LSMR). |
| <0.001 |
| LSM Difference |
| 83.29 |
| 2-Sided |
| 90 |
| 63.9 |
| 102.7 |
Full inhibition is ≥74% inhibition of blood eosinophil CD11b expression at trough |
| Other |