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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: Prednisone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Jasper Clinic, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence A; Period 1: Placebo Period 2: Prednisone 2.5 mg Period 3: Prednisone 10 mg	Drug: Prednisone; 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.; Drug: Placebo; Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.
Other: Sequence B; Period 1: Prednisone 2.5 mg Period 2: Prednisone 5 mg Period 3: Prednisone 20 mg	Drug: Prednisone; 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.
Other: Sequence C; Period 1: Prednisone 5 mg Period 2: Prednisone 10 mg Period 3: Prednisone 40 mg	Drug: Prednisone; 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.
Other: Sequence D; Period 1: Prednisone 10 mg Period 2: Prednisone 20 mg Period 3: Prednisone 60 mg	Drug: Prednisone; 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.
Other: Sequence E; Period 1: Prednisone 20 mg Period 2: Prednisone 40 mg Period 3: Placebo	Drug: Prednisone; 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.; Drug: Placebo; Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.
Other: Sequence F; Period 1: Prednisone 40 mg Period 2: Prednisone 60 mg Period 3: Prednisone 2.5 mg	Drug: Prednisone; 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.
Other: Sequence G; Period 1: Prednisone 60 mg Period 2: Placebo Period 3: Prednisone 5 mg	Drug: Prednisone; 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.; Drug: Placebo; Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Fleishaker DL, Mukherjee A, Whaley FS, Daniel S, Zeiher BG. Safety and pharmacodynamic dose response of short-term prednisone in healthy adult subjects: a dose ranging, randomized, placebo-controlled, crossover study. BMC Musculoskelet Disord. 2016 Jul 16;17:293. doi: 10.1186/s12891-016-1135-3.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: April 21, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (Estimate): May 10, 2016

Study Record Updates

• Last Update Posted (Estimate): May 10, 2016
• Last Update Submitted That Met QC Criteria: May 6, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Glucocorticoids, Biomarkers, Dissociated Agonist of the Glucocorticoid Receptor
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: A9001309