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Phase 3 N=122 Randomized Treatment

Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia

Enrolled (actual)
122
Serious AEs
9.8%
Results posted
Sep 2019
Primary outcome: Primary: Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for 17-OHP — -0.403; -0.172 Z-score — p==0.5521

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Chronocort® (Drug); standard glucocorticoid therapy (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Neurocrine UK Limited
Primary completion
Jul 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for 17-OHP
-0.403; -0.172 =0.5521
SECONDARY
Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for A4
0.113; -0.041 =0.7405
SECONDARY
17-OHP and A4 by Individual Baseline Treatment Strata.
-0.248; -0.061; -0.245; -0.431; -0.320; -0.565 =0.8186
SECONDARY
Number of Participants With 17-OHP and A4 Levels in the Optimal Range at 9:00 at Week 24 Visit
30; 25; 30; 30 =0.9877
SECONDARY
Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Fat Mass and Lean Mass)
-0.575; 0.445; 0.640; 0.234 =0.156
SECONDARY
Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Bone Mineral Density) - Measured at All Sites Except Germany.
-0.001; -0.008 =0.2614

Summary

This study is a parallel arm, randomised, open-label study, including dose titration and admissions for four overnight stays for 24-hour endocrine profiles. It will compare the efficacy, safety and tolerability of Chronocort® with standard glucocorticoid replacement therapy in the treatment of congenital adrenal hyperplasia (CAH) over a treatment period of 6 months. Dose titration decisions in both treatment groups will be made by a central independent physician, blinded to the treatment arm, using information generated from the 24-hour endocrine profiles. Each treatment arm will be subject to the same titration rules throughout the study, ensuring that opportunities for optimisation and control of androgens are the same in both groups.

Eligibility Criteria

Inclusion Criteria

  • Known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-OHP and/or A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids) on a stable glucocorticoid therapy for a minimum of 6 months.
  • Provision of signed written informed consent.
  • Non-pregnant, non-lactating females who are post menopausal, naturally or surgically sterile, or of childbearing potential with a negative urinary pregnancy test and using a medically acceptable method of contraception.
  • Plasma renin activity (PRA) less than 1.5 times the upper limit of normal (ULN) at screening or within 3 months prior to screening, except in subjects who have been diagnosed with hypertension where the renin is not being used to monitor fludrocortisone replacement.
  • Plasma renin activity (PRA) less than 1.5 times the upper limit of normal (ULN) at screening or within 3 months prior to screening, except in subjects who have been diagnosed with hypertension where the renin is not being used to monitor fludrocortisone replacement.

Exclusion Criteria

  • Co-morbid condition requiring daily administration of a medication (or consumption of any material) 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 the ULN).
  • Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
  • Subjects with any other significant medical or psychiatric conditions that in the opinion of the investigator would preclude participation in the trial.
  • History of malignancy (other than basal cell carcinoma successfully treated >6 months prior to entry into the study).
  • Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study.
  • Subjects with a history of bilateral adrenalectomy.
  • Subjects having previously been exposed to Chronocort®.
  • Subjects unable to comply with the requirements of the protocol.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02716818). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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