Healthy Adults
Conditions
Keywords
Glucocorticoids, Biomarkers, Dissociated Agonist of the Glucocorticoid Receptor
Brief summary
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.
Interventions
DRUGPrednisone
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.
DRUGPlacebo
Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Adiponectin | 8 days | Change from baseline in adiponectin will be assessed after 7 days of treatment on Day 8 in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Procollagen type 1-N-Propeptide (P1NP) | 8 days | The change from baseline in serum P1NP after treatment on Day 1 and Day 8 will be assessed in each treatment period |
| 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) | 8 days | Change from baseline in uNTX-1 will be assessed on Day 1 and Day 8 after treatment in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Fasting glucose and insulin | 8 days | Glucose and insulin will be assessed for the change from baseline after 7 days of treatment on Day 8 in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on an Oral Glucose Tolerance Test | Day 6 | 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. |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Triglycerides | 8 days | Change from baseline in triglycerides will be assessed after 7 days of treatment on Day 8 in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Urinary Cortisol Suppression | 7 days | Change from baseline in 24-hour urinary cortisol on Day 7 in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on osteocalcin | 8 days | The change in serum osteocalcin from baseline after treatment on Day 1 and Day 8 will be assessed in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Cortisol Suppression | 8 days | Change from baseline in serum cortisol after treatment on Day 1 and Day 8 in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on HPA Axis Suppression | 14 days after the last study visit in Period 3, if repeat testing required will be done 28 days after first test | Serum cortisol in response to low-dose ACTH Stimulation Test will be completed at the end of Period 3 for each subject |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on White Blood Cell Counts | 8 days | Change from baseline in blood leukocytes (neutrophils, lymphocytes and eosinophils) in each treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Medical Outcomes: Sleep Scale (MOS-Sleep) | 7 days | 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. |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on the Incidence of Adverse Events | 28 days after last dose of study medication in Period 3 | Subjects were monitored throughout the study and queried for adverse events |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Blood Pressure | 8 days | Blood pressure will be assessed for change from baseline after 7 days of treatment on Day 8 in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Weight | 8 days | 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. |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on pulse rate | 8 days | Pulse rate will be assessed for change from baseline after 7 days of treatment on Day 8 in each treatment period |
| Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Profile of Mood State | 7 days | 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). |
Countries
United States
Outcome results
None listed