Trial Outcomes & Findings for A Study on the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics (MK-0000-175) (NCT NCT01193049)

Results Overview

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, nasal exudates (NE) and sputum (SP) were collected, then the concentrations of IL-5 were determined from NE and SP collected after 7 hours and previously at baseline (BL), to derive the fold change (FC) from BL for each participant. The geometric mean (GM) was determined by averaging FC from BL for all analyzed participants.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

11 participants

Primary outcome timeframe

Baseline and 7 hours post-allergen challenge

Results posted on

2015-09-04

Participant Flow

Participant milestones

Participant milestones
Measure	Prednisone, Then Placebo Prednisone in the first double blind treatment period and placebo in the second double blind treatment period	Placebo, Then Prednisone Placebo in the first double blind treatment period and prednisone in the second double blind treatment period
Period 1: Placebo Run-In STARTED	5	6
Period 1: Placebo Run-In COMPLETED	5	6
Period 1: Placebo Run-In NOT COMPLETED	0	0
Washout 1 : 21 Day Washout STARTED	5	6
Washout 1 : 21 Day Washout COMPLETED	5	6
Washout 1 : 21 Day Washout NOT COMPLETED	0	0
Period 2 : Double Blind Crossover STARTED	5	6
Period 2 : Double Blind Crossover COMPLETED	5	6
Period 2 : Double Blind Crossover NOT COMPLETED	0	0
Washout 2 : 21 Day Washout STARTED	5	6
Washout 2 : 21 Day Washout COMPLETED	5	6
Washout 2 : 21 Day Washout NOT COMPLETED	0	0
Period 3 : Double Blind Crossover STARTED	5	6
Period 3 : Double Blind Crossover COMPLETED	5	6
Period 3 : Double Blind Crossover NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study on the Effects of a Single Dose of Prednisone on Biomarkers of Allergen Responses in Asthmatics (MK-0000-175)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=11 Participants All randomized participants
Age, Continuous	33.5 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, nasal exudates (NE) and sputum (SP) were collected, then the concentrations of IL-5 were determined from NE and SP collected after 7 hours and previously at baseline (BL), to derive the fold change (FC) from BL for each participant. The geometric mean (GM) was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in Interleukin-5 (IL-5) Concentration From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Sputum	2.16 Fold Change Interval 1.25 to 3.74	8.60 Fold Change Interval 3.82 to 19.34
Geometric Mean Fold Change From Baseline in Interleukin-5 (IL-5) Concentration From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Nasal Exudate	1.69 Fold Change Interval 0.88 to 3.26	8.63 Fold Change Interval 4.45 to 16.77

PRIMARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-13 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in Interleukin-13 (IL-13) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Sputum	1.57 Fold Change Interval 1.21 to 2.04	5.86 Fold Change Interval 2.57 to 13.36
Geometric Mean Fold Change From Baseline in Interleukin-13 (IL-13) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Nasal Exudate	1.02 Fold Change Interval 0.65 to 1.58	3.29 Fold Change Interval 1.82 to 5.95

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of TARC were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in Thymus and Activation Regulated Chemokine (TARC) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Sputum	1.63 Fold Change Interval 1.22 to 2.17	2.04 Fold Change Interval 1.21 to 3.46
Geometric Mean Fold Change From Baseline in Thymus and Activation Regulated Chemokine (TARC) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Nasal Exudates	1.33 Fold Change Interval 0.88 to 2.01	1.22 Fold Change Interval 0.96 to 1.57

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of Eotaxin-3 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in Eotaxin-3 From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Sputum	1.30 Fold Change Interval 0.67 to 2.51	2.14 Fold Change Interval 1.41 to 3.24
Geometric Mean Fold Change From Baseline in Eotaxin-3 From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Nasal Exudates	0.86 Fold Change Interval 0.56 to 1.31	1.35 Fold Change Interval 0.66 to 2.74

SECONDARY outcome

Timeframe: From 1 to 7 hours post-allergen challenge

Population: As all VRI results showed no allergen or treatment-related signals these results are not presented.

One hour before treatment with prednisone/placebo, participants inhaled for 2 minutes a nebulised solution of metacholine (0.13 ml/min); then one hour after prednisone/placebo treatment were challenged with allergens. From 1 to 7 hours after allergen challenge, ventilatory heterogeneity was assessed by Vibration Response Imaging (VRI) by monitoring the following: inspiration/expiration (I/E) amplitude ratio, I/E duration ratio, synchrony duration, and quantitative lung data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, SP were collected, then the RNA expression profiles of IL-5 and IL-13 genes were determined from SP collected after 7 hours and previously at baseline, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in RNA Expression for Genes Encoding IL-5 and IL-13 From Sputum at 7 Hours Post-allergen Challenge IL-5	4.87 Fold Change Interval 3.2 to 7.39	7.37 Fold Change Interval 5.96 to 9.11
Geometric Mean Fold Change From Baseline in RNA Expression for Genes Encoding IL-5 and IL-13 From Sputum at 7 Hours Post-allergen Challenge IL-13	2.90 Fold Change Interval 2.42 to 3.48	3.93 Fold Change Interval 3.02 to 5.13

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-17 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in Interleukin-17 (IL-17) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Sputum	0.68 Fold Change Interval 0.58 to 0.8	0.83 Fold Change Interval 0.71 to 0.98
Geometric Mean Fold Change From Baseline in Interleukin-17 (IL-17) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Nasal Exudates	0.84 Fold Change Interval 0.48 to 1.46	1.23 Fold Change Interval 1.14 to 1.33

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-1β were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in Interleukin-1β (IL-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Sputum	0.80 Fold Change Interval 0.55 to 1.17	1.34 Fold Change Interval 0.86 to 2.09
Geometric Mean Fold Change From Baseline in Interleukin-1β (IL-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Nasal Exudates	0.19 Fold Change Interval 0.14 to 0.27	0.39 Fold Change Interval 0.24 to 0.63

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: All randomized participants

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of MIP-1β were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome measures
Measure	Prednisone n=11 Participants All participants who received at least one dose of prednisone	Placebo n=11 Participants All participants who received at least one dose of placebo
Geometric Mean Fold Change From Baseline in Macrophage Inflammatory Protein-1β (MIP-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Sputum	1.35 Fold Change Interval 0.75 to 2.43	1.92 Fold Change Interval 0.94 to 3.93
Geometric Mean Fold Change From Baseline in Macrophage Inflammatory Protein-1β (MIP-1β) From Nasal Exudates and Sputum at 7 Hours Post-allergen Challenge Nasal Exudates	0.73 Fold Change Interval 0.47 to 1.13	1.19 Fold Change Interval 0.7 to 2.01

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: As TSLP levels were too low to detect, this analysis was not performed and results are not presented.

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of TSLP were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: As IL-23 levels were too low to detect, this analysis was not performed and results are not presented.

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then the concentrations of IL-23 were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was plan to be determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 23 hours post-allergen challenge

Population: As concentrations of cytokines were below the lower limit of quantitation this analysis was not performed, and results are not presented.

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 23 hours had elapsed, BALf were collected, then the concentrations of IL-5, IL-13, and TARC were determined from BALf collected after 23 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 7 hours post-allergen challenge

Population: As this same approach in a parallel study was unfruitful, these data were not pursued, and results are not presented.

Participants were treated with either prednisone or placebo, followed 1 hour later by nasal allergen challenge and then inhaled allergen challenge. After 7 hours had elapsed, NE and SP were collected, then prostaglandin and leukotriene concentrations were determined from NE and SP collected after 7 hours and previously at BL, to derive the FC from BL for each participant. The GM was planned to be determined by averaging FC from BL for all analyzed participants.

Outcome measures

Outcome data not reported

Adverse Events

Prednisone

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Prednisone n=11 participants at risk All participants who received at least one dose of prednisone	Placebo n=11 participants at risk All participants who received at least one dose of placebo
Gastrointestinal disorders Nausea	0.00% 0/11 All participants in this crossover study received both prednisone and placebo.	9.1% 1/11 All participants in this crossover study received both prednisone and placebo.
Gastrointestinal disorders Vomiting	0.00% 0/11 All participants in this crossover study received both prednisone and placebo.	9.1% 1/11 All participants in this crossover study received both prednisone and placebo.
General disorders Influenza Like Illness	9.1% 1/11 All participants in this crossover study received both prednisone and placebo.	0.00% 0/11 All participants in this crossover study received both prednisone and placebo.
Immune system disorders Seasonal Allergy	0.00% 0/11 All participants in this crossover study received both prednisone and placebo.	9.1% 1/11 All participants in this crossover study received both prednisone and placebo.
Injury, poisoning and procedural complications Wrist Fracture	0.00% 0/11 All participants in this crossover study received both prednisone and placebo.	9.1% 1/11 All participants in this crossover study received both prednisone and placebo.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/11 All participants in this crossover study received both prednisone and placebo.	9.1% 1/11 All participants in this crossover study received both prednisone and placebo.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp and Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER