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

NCT02767089 | Completed Phase 1

• 1 other identifier: A9001309
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Adults

Keywords

Glucocorticoids, Biomarkers, Dissociated Agonist of the Glucocorticoid Receptor

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (6)

• Characterize the dose-response effect of prednisone 2.5, 5, 10, 20, 40 and 60 mg on Profile of Mood State

  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)

  7 days

• 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 Weight

  8 days

Study Arms (7)

Sequence A

OTHER

Period 1: Placebo Period 2: Prednisone 2.5 mg Period 3: Prednisone 10 mg

Drug: Prednisone; Drug: Placebo

Sequence B

OTHER

Period 1: Prednisone 2.5 mg Period 2: Prednisone 5 mg Period 3: Prednisone 20 mg

Drug: Prednisone

Sequence C

OTHER

Period 1: Prednisone 5 mg Period 2: Prednisone 10 mg Period 3: Prednisone 40 mg

Drug: Prednisone

Sequence D

OTHER

Period 1: Prednisone 10 mg Period 2: Prednisone 20 mg Period 3: Prednisone 60 mg

Drug: Prednisone

Sequence E

OTHER

Period 1: Prednisone 20 mg Period 2: Prednisone 40 mg Period 3: Placebo

Drug: Prednisone; Drug: Placebo

Sequence F

OTHER

Period 1: Prednisone 40 mg Period 2: Prednisone 60 mg Period 3: Prednisone 2.5 mg

Drug: Prednisone

Sequence G

OTHER

Period 1: Prednisone 60 mg Period 2: Placebo Period 3: Prednisone 5 mg

Drug: Prednisone; Drug: Placebo

Interventions

Prednisone DRUG

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.

Sequence A; Sequence B; Sequence C; Sequence D; Sequence E; Sequence F; Sequence G

Placebo DRUG

Placebo tablets similar to Prednisone 2.5 mg and 20 mg were supplied to make the trial doses.

Sequence A; Sequence E; Sequence G

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or females willing to be confined and comply with scheduled visits
• Women are to be surgically sterile.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Jasper Clinic, Inc.

Kalamazoo, Michigan, 49007, United States

Location

Related Publications (1)

• 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.

  PMID: 27424036 DERIVED

MeSH Terms

Interventions

Prednisone

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2016
• First Posted: May 10, 2016
• Study Start: October 1, 2005
• Primary Completion: March 1, 2006
• Study Completion: March 1, 2006
• Last Updated: May 10, 2016

Record last verified: 2016-05

Locations

US (1)