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Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH

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ClinicalTrials.gov Identifier: NCT01735617
Recruitment Status : Completed
First Posted : November 28, 2012
Results First Posted : May 17, 2017
Last Update Posted : May 17, 2017
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Diurnal Limited

Tracking Information
First Submitted Date  ICMJE November 20, 2012
First Posted Date  ICMJE November 28, 2012
Results First Submitted Date  ICMJE June 25, 2015
Results First Posted Date  ICMJE May 17, 2017
Last Update Posted Date May 17, 2017
Study Start Date  ICMJE December 2012
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2017)
  • Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia [ Time Frame: 24 hours ]
    The maximum plasma concentration (Cmax) of chronocort
  • Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia [ Time Frame: 24 hours (at 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs) ]
    Area under the curve (AUC) from 0 to 24 hours (sampling occurs at the following timepoints: 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs)
  • Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia [ Time Frame: 24 hours ]
    Time to maximum plasma concentration (tmax)
Original Primary Outcome Measures  ICMJE
 (submitted: November 25, 2012)
Pharmacokinetic profile following short-term treatment with Chronocort® in adult patients with congenital adrenal hyperplasia [ Time Frame: Single-dose (24-hour) ]
Area under the plasma concentration versus time curve (AUC) of Chronocort sampled at the following time-points post dosing: 0,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,20,24-hours
Change History Complete list of historical versions of study NCT01735617 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2017)
  • The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline) [ Time Frame: Specific time point (0700hrs) ]
    Proposed optimal ranges of 17-OHP: 300-1200ng/dl Proposed optimal ranges of androstenedione: 40-150ng.dl for males and 30-200ng/dl for females
  • 17-OHP Levels at 0700h, 1700h and 2300h [ Time Frame: Specified time points (0700h, 1700h and 2300h) ]
    17-OHP levels at 0700h, 1700h and 2300h
  • Androstenedione Levels at 0700h, 1700h and 2300h [ Time Frame: Specified time points (0700h, 1700h and 2300h) ]
    Androstenedione levels at 0700h, 1700h and 2300h
  • ACTH Levels at 0700h, 1700h and 2300h [ Time Frame: Specified time points (0700h, 1700h and 2300h) ]
    ACTH levels at 0700h, 1700h and 2300h
  • AUC Values (Nmol*h/L) for Androstenedione [ Time Frame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) ]
    AUC values (nmol*h/L) for Androstenedione for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
  • AUC Values (Nmol*h/L) for 17-OHP [ Time Frame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) ]
    AUC values (nmol*h/L) for 17-OHP for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
  • AUC Values (Pmol*h/L) for ACTH [ Time Frame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) ]
    AUC values (pmol*h/L) for ACTH for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
Original Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2012)
  • Assessment of efficacy profile of Chronocort in relation to 17-hydroxyprogesterone level [ Time Frame: 6-months ]
    Percentage of patients with 17-hydroxyprogesterone (17-OHP) level within proposed optimal range after 2, 4 and 6-months on Chronocort relative to pre-dose baseline
  • Assessment of efficacy profile of Chronocort in relation androstenedione level [ Time Frame: 6-months ]
    Percentage change in androstenedione levels after 2, 4 and 6-months on Chronocort relative to pre-dose baseline
  • Assessment of efficacy profile of Chronocort in relation to adrenocorticotrophic hormone level [ Time Frame: 6-months ]
    Percentage change in adrenocorticotrophic (ACTH) level after 2, 4 and 6-months on Chronocort relative to pre-dose baseline
  • Assessment of efficacy profile of Chronocort in relation to urinary steroidal level [ Time Frame: 6-months ]
    Percentage change in urinary steroidal level after 2, 4 and 6-months on Chronocort relative to pre-dose baseline
  • Assessment of efficacy profile of Chronocort in relation to fasting insulin level [ Time Frame: 6-months ]
    Percentage change in fasting insulin level 2, 4, 6-months on Chronocort relative to pre-dose baseline
  • Assessment of efficacy profile of Chronocort in relation to bone turnover marker serum [ Time Frame: 6-months ]
    Percentage change in bone turnover marker serum, osteocalcin, after 2, 4, 6-months on Chronocort relative to pre-dose baseline
  • Assessment of efficacy profile of Chronocort in relation to blood glucose level [ Time Frame: 6-months ]
    Percentage change in blood glucose level 2, 4, 6-months on Chronocort relative to pre-dose baseline
  • Assessment of efficacy profile of Chronocort in relation to body mass index [ Time Frame: 6-months ]
    Percentage change in body mass index after 2, 4, 6-months on Chronocort relative to pre-dose baseline
  • Assessment of safety profile of Chronocort in relation to reported adverse events [ Time Frame: 6-months ]
    Number of reported adverse events following 6-months treatment with Chronocort
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH
Official Title  ICMJE A Phase 2 Pilot Study to Characterize and Examine the Pharmacokinetics and Disease Bio-marker Response of Chronocort® in Adults With Congenital Adrenal Hyperplasia
Brief Summary The purpose of this study is to gather safety and effectiveness information about a new formulation of Hydrocortisone (Chronocort®) used to treat patients with a disease called congenital adrenal hyperplasia (CAH). Hydrocortisone is the man-made version of the hormone cortisol, which is released in the body following a regular daily pattern. The objective of the study is to measure the levels of hydrocortisone that are absorbed into the bloodstream once Chronocort® is taken and what affects it has on other hormones in the body. Since Chronocort® is anticipated to mimic the same release pattern of cortisol in the body, it is hoped that patients with CAH will be treated more effectively to manage their disease.
Detailed Description This study is a Phase 2 pilot study to characterize and examine the pharmacokinetics and efficacy profile of Chronocort® in adults with congenital adrenal hyperplasia (CAH). It is designed as a two-part, single cohort, open label, multiple dose Phase 2 pilot study to: (Part A) characterize and examine the pharmacokinetics (PK) and disease bio-marker behavior following short-term dosing with Chronocort®; and to (Part B) examine the disease control after six months dose titration with Chronocort® in adults with CAH.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Endocrine Disease
  • Adrenal Insufficiency
  • Congenital Adrenal Hyperplasia
Intervention  ICMJE Drug: Hydrocortisone Modified Release Capsules
Patients with congenital adrenal hyperplasia standardised on conventional therapy is enrolled onto the study and treatment is switched to Chronocort, initially for pharmacokinetic assessment followed by longer-term biochemical and efficacy assessment
Other Name: Chronocort
Study Arms  ICMJE Experimental: Hydrocortisone Modified Release Capsules
Chronocort Modified Release Capsules, 5mg, 10mg and 20mg Dosing frequency twice-daily (mane and nocte) Dose setting by titration to achieve optimal biochemical and therapeutic response
Intervention: Drug: Hydrocortisone Modified Release Capsules
Publications * Mallappa A, Sinaii N, Kumar P, Whitaker MJ, Daley LA, Digweed D, Eckland DJ, Van Ryzin C, Nieman LK, Arlt W, Ross RJ, Merke DP. A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2015 Mar;100(3):1137-45. doi: 10.1210/jc.2014-3809. Epub 2014 Dec 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 25, 2012)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Known CAH due to 21-hydroxylase deficiency (classic CAH) based on hormonal and genetic testing currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone on a stable dosage for a minimum of 3 months.
  2. Male or female patients aged 18 and above.
  3. Provision of signed written informed consent.
  4. Good general health.
  5. Females of childbearing potential must have a negative pregnancy test initially and at all visits. Females who are engaging in sexual intercourse must be using a medically acceptable method of contraception (as defined in the protocol, section 10.5).
  6. Plasma renin activity must be within the clinically acceptable range at screening (less than 1.5 times upper normal range).

Exclusion Criteria:

  1. Co-morbid condition requiring daily administration of a medication that induces hepatic enzymes or interferes with the metabolism of glucocorticoids.
  2. Clinical or biochemical evidence of hepatic or renal disease. Creatinine above the normal range or elevated liver function tests (ALT or AST) > 2 times the upper limits of normal.
  3. Females who are pregnant or lactating.
  4. Women taking an estrogen-containing oral contraceptive pill and who have taken it within 6 weeks of recruitment.
  5. Patients taking spironolactone.
  6. Patients on inhaled or oral steroids apart from treatment for CAH.
  7. Patients with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the trial.
  8. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study.
  9. Patients with history of bilateral adrenalectomy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01735617
Other Study ID Numbers  ICMJE DIUR-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Diurnal Limited
Study Sponsor  ICMJE Diurnal Limited
Collaborators  ICMJE National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Deborah P Merke, BS, MS, MD National Institutes of Health Clinical Center (CC)
PRS Account Diurnal Limited
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP