A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH
Study Details
Study Description
Brief Summary
Subjects completing study DIUR-005 and those who have already completed study DIUR-003 will be offered the opportunity either to continue Chronocort® therapy or to switch from their current glucocorticoid therapy to Chronocort® in this open-label study.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
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 Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be withdrawn from this study.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 Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Chronocort® Chronocort® modified release hydrocortisone |
Drug: Hydrocortisone
Modified release hydrocortisone
|
Outcome Measures
Primary Outcome Measures
- Safety and tolerability of Chronocort over time, as assessed by signs and symptoms of adrenal insufficiency. [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.
- Safety and tolerability of Chronocort, as assessed by incidence of use of sick day rules. [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.
- Safety and tolerability of Chronocort, as assessed by the occurrence of adrenal crises. [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.
- Safety and tolerability of Chronocort, as assessed by the occurrence of adverse events (AEs). [5.5 years]
Safety and tolerability of Chronocort, as assessed by the occurrence of AEs throughout the study.
- Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort® baseline in safety laboratory assessments. [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.
- Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort® baseline in vital signs, weight, body mass index (BMI) and waist circumference. [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.
Secondary Outcome Measures
- Long-term efficacy of Chronocort, as assessed by total daily dose of Chronocort in mg/day of hydrocortisone and by Body Surface Area (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 total daily dose of Chronocort in mg/day of hydrocortisone during the study, and by BSA.
- Long-term efficacy of Chronocort, as assessed by serum 17-OHP levels. [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.
- Long-term efficacy of Chronocort, as assessed by serum A4 levels [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.
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in Standarad Deviation Score (SDS) of 17-OHP. [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.
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in SDS of A4. [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.
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in absolute values of 17-OHP. [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).
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline in absolute values of A4. [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).
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in bone turnover markers [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).
- 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 at each visit in total Testosterone
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline in fasting insulin, blood glucose levels, and HbA1c. [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.
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in hsCRP and PRA [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
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in body composition. [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).
- Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in Quality of Life [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.
- 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)]
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort® baseline at each visit in incidence of dose titrations.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | National Institutes of Health Clinical Center | Bethesda | Maryland | United States | 20892-1932 |
Sponsors and Collaborators
- Diurnal Limited
Investigators
- Principal Investigator: Debbie Merke, MD, National Institutes of Health (NIH)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DIUR-006