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
Overview
- Phase
- Phase 1
- Intervention
- Prednisone
- Conditions
- Healthy Adults
- Sponsor
- Pfizer
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Cortisol Suppression
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Sequence A
Period 1: Placebo Period 2: Prednisone 2.5 mg Period 3: Prednisone 10 mg
Intervention: Prednisone
Sequence A
Period 1: Placebo Period 2: Prednisone 2.5 mg Period 3: Prednisone 10 mg
Intervention: Placebo
Sequence B
Period 1: Prednisone 2.5 mg Period 2: Prednisone 5 mg Period 3: Prednisone 20 mg
Intervention: Prednisone
Sequence C
Period 1: Prednisone 5 mg Period 2: Prednisone 10 mg Period 3: Prednisone 40 mg
Intervention: Prednisone
Sequence D
Period 1: Prednisone 10 mg Period 2: Prednisone 20 mg Period 3: Prednisone 60 mg
Intervention: Prednisone
Sequence E
Period 1: Prednisone 20 mg Period 2: Prednisone 40 mg Period 3: Placebo
Intervention: Prednisone
Sequence E
Period 1: Prednisone 20 mg Period 2: Prednisone 40 mg Period 3: Placebo
Intervention: Placebo
Sequence F
Period 1: Prednisone 40 mg Period 2: Prednisone 60 mg Period 3: Prednisone 2.5 mg
Intervention: Prednisone
Sequence G
Period 1: Prednisone 60 mg Period 2: Placebo Period 3: Prednisone 5 mg
Intervention: Prednisone
Sequence G
Period 1: Prednisone 60 mg Period 2: Placebo Period 3: Prednisone 5 mg
Intervention: Placebo
Outcomes
Primary Outcomes
Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Cortisol Suppression
Time Frame: 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 osteocalcin
Time Frame: 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 Procollagen type 1-N-Propeptide (P1NP)
Time Frame: 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 Triglycerides
Time Frame: 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 Adiponectin
Time Frame: 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 White Blood Cell Counts
Time Frame: 8 days
Change from baseline in blood leukocytes (neutrophils, lymphocytes and eosinophils) 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
Time Frame: 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 HPA Axis Suppression
Time Frame: 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 Fasting glucose and insulin
Time Frame: 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 Urinary Cortisol Suppression
Time Frame: 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 Urinary N-terminal cross-linked telopeptide of type 1 collagen (uNTX-1)
Time Frame: 8 days
Change from baseline in uNTX-1 will be assessed on Day 1 and Day 8 after treatment in each treatment period
Secondary Outcomes
- 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)
- Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Blood Pressure(8 days)
- 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)
- Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on pulse rate(8 days)
- Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Weight(8 days)
- Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Profile of Mood State(7 days)