The Dose Response of Prednisone on Biochemical and Clinical Makers in Adult Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to further access the utility of biochemical and clinical biomarkers for glucocorticoid-mediated anti-inflammatory effects and safety endpoints against which dissociated agonists of the glucocorticoid receptor (DAGR) will be evaluated in adult healthy volunteers.

Official Title
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A Randomized, Single-blind, Placebo-controlled, Crossover Studyto Assess The Dose Response Of Prednisone On Biochemical Andclinical Markers Of Efficacy And Safety In Adult Healthyvolunteers

Conditions
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Healthy Adults

Intervention / Treatment
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* Drug: Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or females willing to be confined and comply with scheduled visits Women are to be surgically sterile. Exclusion Criteria: History of febrile illness within 5 days prior to the first dose Positive urine drug screen Treatment with an investigational product within 30 days prior to the first dose of study medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sequence A<br>Period 1: Placebo Period 2: Prednisone 2.5 mg Period 3: Prednisone 10 mg | Drug: Prednisone<br>* Subjects will receive oral prednisone and/or placebo tablets (total of 4 tablets) to achieve the required dose according to the treatment sequence group they were randomized. Subjects are to be dosed each morning for 7 days. A 14 day washout period is required between each period. Prednisone was supplied in the 2.5 and 20 mg dosage strengths.<br>Drug: Placebo<br>* Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.<br>|
| Other: Sequence B<br>Period 1: Prednisone 2.5 mg Period 2: Prednisone 5 mg Period 3: Prednisone 20 mg | Drug: Prednisone<br>* Subjects will receive oral prednisone and/or placebo tablets (total of 4 tablets) to achieve the required dose according to the treatment sequence group they were randomized. Subjects are to be dosed each morning for 7 days. A 14 day washout period is required between each period. Prednisone was supplied in the 2.5 and 20 mg dosage strengths.<br>|
| Other: Sequence C<br>Period 1: Prednisone 5 mg Period 2: Prednisone 10 mg Period 3: Prednisone 40 mg | Drug: Prednisone<br>* Subjects will receive oral prednisone and/or placebo tablets (total of 4 tablets) to achieve the required dose according to the treatment sequence group they were randomized. Subjects are to be dosed each morning for 7 days. A 14 day washout period is required between each period. Prednisone was supplied in the 2.5 and 20 mg dosage strengths.<br>|
| Other: Sequence D<br>Period 1: Prednisone 10 mg Period 2: Prednisone 20 mg Period 3: Prednisone 60 mg | Drug: Prednisone<br>* Subjects will receive oral prednisone and/or placebo tablets (total of 4 tablets) to achieve the required dose according to the treatment sequence group they were randomized. Subjects are to be dosed each morning for 7 days. A 14 day washout period is required between each period. Prednisone was supplied in the 2.5 and 20 mg dosage strengths.<br>|
| Other: Sequence E<br>Period 1: Prednisone 20 mg Period 2: Prednisone 40 mg Period 3: Placebo | Drug: Prednisone<br>* Subjects will receive oral prednisone and/or placebo tablets (total of 4 tablets) to achieve the required dose according to the treatment sequence group they were randomized. Subjects are to be dosed each morning for 7 days. A 14 day washout period is required between each period. Prednisone was supplied in the 2.5 and 20 mg dosage strengths.<br>Drug: Placebo<br>* Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.<br>|
| Other: Sequence F<br>Period 1: Prednisone 40 mg Period 2: Prednisone 60 mg Period 3: Prednisone 2.5 mg | Drug: Prednisone<br>* Subjects will receive oral prednisone and/or placebo tablets (total of 4 tablets) to achieve the required dose according to the treatment sequence group they were randomized. Subjects are to be dosed each morning for 7 days. A 14 day washout period is required between each period. Prednisone was supplied in the 2.5 and 20 mg dosage strengths.<br>|
| Other: Sequence G<br>Period 1: Prednisone 60 mg Period 2: Placebo Period 3: Prednisone 5 mg | Drug: Prednisone<br>* Subjects will receive oral prednisone and/or placebo tablets (total of 4 tablets) to achieve the required dose according to the treatment sequence group they were randomized. Subjects are to be dosed each morning for 7 days. A 14 day washout period is required between each period. Prednisone was supplied in the 2.5 and 20 mg dosage strengths.<br>Drug: Placebo<br>* Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on osteocalcin | The change in serum osteocalcin from baseline after treatment on Day 1 and Day 8 will be assessed in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Cortisol Suppression | Change from baseline in serum cortisol after treatment on Day 1 and Day 8 in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on HPA Axis Suppression | Serum cortisol in response to low-dose ACTH Stimulation Test will be completed at the end of Period 3 for each subject | 14 days after the last study visit in Period 3, if repeat testing required will be done 28 days after first test | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on White Blood Cell Counts | Change from baseline in blood leukocytes (neutrophils, lymphocytes and eosinophils) in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Procollagen type 1-N-Propeptide (P1NP) | The change from baseline in serum P1NP after treatment on Day 1 and Day 8 will be assessed in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Urinary N-terminal cross-linked telopeptide of type 1 collagen (uNTX-1) | Change from baseline in uNTX-1 will be assessed on Day 1 and Day 8 after treatment in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Fasting glucose and insulin | Glucose and insulin will be assessed for the change from baseline after 7 days of treatment on Day 8 in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on an Oral Glucose Tolerance Test | On Day 6 of each period, subjects will undergo an oral glucose tolerance test. After ingesting 75 g of a glucose solution within 5 minutes of receiving their daily dose of prednisone, blood samples for glucose were obtained at 0.5, 1 and 2 hours. | Day 6 | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Triglycerides | Change from baseline in triglycerides will be assessed after 7 days of treatment on Day 8 in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Urinary Cortisol Suppression | Change from baseline in 24-hour urinary cortisol on Day 7 in each treatment period | 7 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Adiponectin | Change from baseline in adiponectin will be assessed after 7 days of treatment on Day 8 in each treatment period | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Profile of Mood State | Change from baseline after 7 days of treatment in each treatment period. The POMS is a copyrighted questionnaire that measures 6 dimensions of mood. The subject will assess how 65 descriptors apply to him/her on a 5-point scale of 0 (not at all) to 4 (extremely). | 7 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Medical Outcomes: Sleep Scale (MOS-Sleep) | Change from baseline in sleep after 7 days of treatment will be assessed in each treatment period. The patient-reported questionnaire consists of 12 items that assesses the key constructs of sleep. Scores can range from 12-71 with higher number indicating more problems with sleep. | 7 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on the Incidence of Adverse Events | Subjects were monitored throughout the study and queried for adverse events | 28 days after last dose of study medication in Period 3 | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Blood Pressure | Blood pressure will be assessed for change from baseline after 7 days of treatment on Day 8 in each treatment period | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Weight | A post-void weight will be collected on the morning of Day 1 and Day 8 to assess change from baseline during each treatment period. | 8 days | 
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on pulse rate | Pulse rate will be assessed for change from baseline after 7 days of treatment on Day 8 in each treatment period | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoids, Biomarkers, Dissociated Agonist of the Glucocorticoid Receptor