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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01735617
First Posted: November 28, 2012
Last Update Posted: May 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Diurnal Limited
  Purpose
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.

Condition Intervention Phase
Endocrine Disease Adrenal Insufficiency Congenital Adrenal Hyperplasia Drug: Hydrocortisone Modified Release Capsules Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Pilot Study to Characterize and Examine the Pharmacokinetics and Disease Bio-marker Response of Chronocort® in Adults With Congenital Adrenal Hyperplasia

Resource links provided by NLM:


Further study details as provided by Diurnal Limited:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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


Enrollment: 16
Study Start Date: December 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01735617


Locations
United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892-1932
Sponsors and Collaborators
Diurnal Limited
National Institutes of Health (NIH)
Investigators
Principal Investigator: Deborah P Merke, BS, MS, MD National Institutes of Health Clinical Center (CC)
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Diurnal Limited
ClinicalTrials.gov Identifier: NCT01735617     History of Changes
Other Study ID Numbers: DIUR-003
First Submitted: November 20, 2012
First Posted: November 28, 2012
Results First Submitted: June 25, 2015
Results First Posted: May 17, 2017
Last Update Posted: May 17, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Diurnal Limited:
congenital adrenal hyperplasia
glucocorticoids
cortisol
adrenal

Additional relevant MeSH terms:
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Hyperplasia
Adrenal Insufficiency
Adrenocortical Hyperfunction
Endocrine System Diseases
Pathologic Processes
Adrenal Gland Diseases
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Gonadal Disorders
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Epinephrine
Racepinephrine
Epinephryl borate
Anti-Inflammatory Agents
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs