- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03062280
A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH
A Phase III Extension Study of Efficacy, Safety and Tolerability of Chronocort® in the Treatment of Congenital Adrenal Hyperplasia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
All subjects will have a screening visit prior to the baseline assessment to allow DIUR-006 procedures to be fully explained and informed consent to be given by the subject. For subjects from DIUR-003 this screening visit will include safety blood tests. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be not be entered into the study.
All subjects will then return for the baseline visit. For subjects entering from study DIUR-003 the full set of baseline assessments will be completed, including 2 blood samples (one at 09:00 and one at 13:00 hours) for 17-OHP and A4. For subjects entering from DIUR-005, test results from their last visit in the feeder study (Visit 4) will be used for this baseline assessment, with the 09:00 and 13:00 hour results taken from the 24-hour hormone profiles conducted at the visit. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be withdrawn from this study.
Once the baseline assessments are completed, the subjects will be given sufficient Chronocort® to use until the next visit at Week 4. Subjects from study DIUR-005 who were previously on Chronocort® will continue on the same dose of Chronocort® that they were receiving at the end of the feeder study. Subjects from study DIUR-005 on standard therapy and subjects from study DIUR-003 will have their initial dose of Chronocort® determined using the hydrocortisone equivalent of baseline therapy.
All subjects will return to the study centre at 4, 12 and 24 weeks after starting study DIUR-006 for additional blood tests and dose titration, if necessary. Visits thereafter will take place at 6-monthly intervals. If there is a change of dose, an interim visit or phone call will be needed inbetween the 6-monthly visits.
All subjects will receive telephone calls at 3 monthly intervals, and unscheduled visits will be arranged if necessary. Subjects will also be provided with Chronocort® supplies from the study pharmacy at 3-monthly or 6-monthly intervals.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Maryland
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Bethesda, Maryland, United States, 20892-1932
- National Institutes of Health Clinical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects with CAH who have successfully completed a clinical trial with the current formulation of Chronocort®.
- Provision of signed written informed consent.
Exclusion Criteria:
- Co-morbid condition requiring daily administration of a medication (or use of any medications/supplements) that interferes with the metabolism of glucocorticoids.
- Clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the ULN or elevated liver function tests (ALT or AST >2 times ULN]).
- Females who are pregnant or lactating.
- Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
- History of malignancy (other than basal cell carcinoma successfully treated >6 months prior to entry into the study).
- Subjects with a history of bilateral adrenalectomy.
- Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study, except for another clinical trial with the current formulation of Chronocort®.
- Subjects unable to comply with the requirements of the protocol.
- Subjects who routinely work night shifts and so do not sleep during the usual nighttime hours.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Chronocort®
Chronocort® modified release hydrocortisone
|
Modified release hydrocortisone
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of Chronocort over time, as assessed by signs and symptoms of adrenal insufficiency.
Time Frame: 5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months and final visit)
|
Safety and tolerability of Chronocort® over time, as assessed by signs and symptoms of adrenal insufficiency or over-treatment throughout the study.
|
5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months and final visit)
|
Safety and tolerability of Chronocort, as assessed by incidence of use of sick day rules.
Time Frame: 5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months and final visit)
|
Safety and tolerability of Chronocort, as assessed by incidence of use of sick day rules throughout the study.
|
5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months and final visit)
|
Safety and tolerability of Chronocort, as assessed by the occurrence of adrenal crises.
Time Frame: 5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months and final visit)
|
Safety and tolerability of Chronocort, as assessed by the occurrence of adrenal crises throughout the study.
|
5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months and final visit)
|
Safety and tolerability of Chronocort, as assessed by the occurrence of adverse events (AEs).
Time Frame: 5.5 years
|
Safety and tolerability of Chronocort, as assessed by the occurrence of AEs throughout the study.
|
5.5 years
|
Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort® baseline in safety laboratory assessments.
Time Frame: 5.5 years (Assessed at visits: Screening [V0], Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort® baseline in safety laboratory assessments throughout the study.
|
5.5 years (Assessed at visits: Screening [V0], Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort® baseline in vital signs, weight, body mass index (BMI) and waist circumference.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort® baseline in vital signs, weight, body mass index (BMI) and waist circumference throughout the study.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Long-term efficacy of Chronocort, as assessed by total daily dose of Chronocort in mg/day of hydrocortisone and by Body Surface Area (BSA).
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by total daily dose of Chronocort in mg/day of hydrocortisone during the study, and by BSA.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by serum 17-OHP levels.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by serum 17-OHP levels, when measured at two time points (at 09:00 and 13:00 hours at each study visit) to assess disease control in the optimal range at both time points, and by the proportion of dose given at night.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by serum A4 levels
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by serum A4 levels, when measured at two time points (at 09:00 and 13:00 hours at each study visit) to assess disease control in the normal range at both time points, and by the proportion of dose given at night.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in Standarad Deviation Score (SDS) of 17-OHP.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in SDS of 17-OHP, when measured at two time points (at 09:00 and 13:00 hours at each study visit) and the mean of the two timepoints.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in SDS of A4.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in SDS of A4, when measured at two time points (at 09:00 and 13:00 hours at each study visit) and the mean of the two timepoints.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in absolute values of 17-OHP.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in absolute values of 17-OHP, when measured at two time points (09:00 and 13:00 hours at each study visit).
|
5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in absolute values of A4.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in absolute values of A4, when measured at two time points (09:00 and 13:00 hours at each study visit).
|
5.5 years (Assessed at visits: Baseline [V1], Visit 2, Visit 3, Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in bone turnover markers
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in bone turnover markers (CTX and osteocalcin).
|
5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in total Testosterone
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
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Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in total Testosterone
|
5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline in fasting insulin, blood glucose levels, and HbA1c.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline in fasting insulin, blood glucose levels, and HbA1c at each visit.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in hsCRP and PRA
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline in hsCRP and PRA at each visit
|
5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in body composition.
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline in body composition (DEXA)(fat mass, lean mass and total bone density) (except in Germany).
|
5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in Quality of Life
Time Frame: 5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Change from pre-Chronocort® baseline at each visit in Quality of Life, as assessed by SF-36, MAF and EQ-5D.
|
5.5 years (Assessed at visits: Baseline [V1], Visit 4 then every 6 months and Final visit)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in incidence of dose titrations.
Time Frame: 5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months)
|
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in incidence of dose titrations.
|
5.5 years (Assessed at visits: Visit 2, Visit 3, Visit 4 then every 6 months)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Endocrine System Diseases
- Gonadal Disorders
- Disorders of Sex Development
- Urogenital Abnormalities
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Adrenal Gland Diseases
- Steroid Metabolism, Inborn Errors
- Hyperplasia
- Adrenal Hyperplasia, Congenital
- Adrenogenital Syndrome
- Anti-Inflammatory Agents
- Hydrocortisone
Other Study ID Numbers
- DIUR-006
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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