A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH

NCT03062280 | Completed Phase 3 Results DMC

• 1 other identifier: DIUR-006
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Adrenal Hyperplasia

Keywords

Extension study

Outcome Measures

Primary Outcomes (14)

• Safety and Tolerability - Number of Participants With Adrenal Insufficiency

  Safety and tolerability of Chronocort® over time, as assessed by signs and symptoms of adrenal insufficiency or over-treatment throughout the study. Signs and symptoms of adrenal insufficiency included sudden weight loss, sudden weight gain, lack of appetite, increased appetite, nausea, vomiting, headache, blurred vision, fatigue, weakness, dizziness, light-headedness, syncope, sleeping difficulties and increased acne. Number of participants who experienced adrenal insufficiency due to glucocorticoid (GC) over replacement and under replacement are reported.

  Up to approximately 5 years and 11 months

• Safety and Tolerability - Number of Participants Who Used Sick Day Medication

  Safety and tolerability of Chronocort, as assessed by number of participants who used sick day medication throughout the study. Data are presented for number of participants taking medication from sick day packs and number of participants taking medication that was not from sick day packs.

  Up to approximately 5 years and 11 months

• Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis

  Safety and tolerability of Chronocort, as assessed by the number of participants who experienced adrenal crises throughout the study. Adrenal crisis was defined as follows: a) Major impairment of general health with at least two of the following signs/symptoms: Hypotension (systolic blood pressure \<100 mmHg); Nausea or vomiting; Severe fatigue; Fever; Somnolence; Hyponatraemia (\<132 mmol/L) or hyperkalaemia (as judged by characteristic electrocardiogram \[ECG\] changes); Hypoglycaemia and b) Parenteral glucocorticoid (hydrocortisone) administration followed by clinical improvement: Grade 1: outpatient care only; Grade 2: hospital care (general ward); Grade 3: admission to intensive care unit; Grade 4: death from adrenal crisis (with or without parenteral glucocorticoid administration).

  Up to approximately 5 years and 11 months

• Safety and Tolerability - Number of Participants With Adverse Events (AEs)

  Safety and tolerability of Chronocort, as assessed by the number of participants with at least 1 AE per specified AE category throughout the study. An AE was any untoward medical occurrence in a participant administered the study drug that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, was a congenital anomaly or birth defect, was infection that required treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement might jeopardize the participants, or might require medical or surgical intervention to prevent any of the above. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

  Up to approximately 5 years and 11 months

• Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values

  Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline in safety laboratory assessments throughout the study. Participants with a parameter value that shifted from baseline (within reference range) to a value above the reference range for a maximum value on-treatment.

  Baseline up to approximately 5 years and 11 months

• Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values

  Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline in safety laboratory assessments throughout the study. Participants with a parameter value that shifted from baseline (within reference range) to a value below the reference range for a minimum value on-treatment.

  Baseline up to approximately 5 years and 11 months

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Diastolic Blood Pressure

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Diastolic blood pressure.

  Baseline, Month 30

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Systolic Blood Pressure

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Systolic blood pressure.

  Baseline, Month 30

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Pulse Rate

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Pulse rate.

  Baseline, Month 30

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Respiratory Rate

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Respiratory rate.

  Baseline, Month 30

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - body temperature.

  Baseline, Month 30

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Body Weight.

  Baseline, Month 30

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - BMI

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - BMI.

  Baseline, Month 30

• Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference

  Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Waist circumference.

  Baseline, Month 30

Secondary Outcomes (19)

• Total Daily Dose of Chronocort in Milligrams (mg)/Day of Hydrocortisone During the Time Interval Baseline to Week 4 and Month 18 to Month 24

  Baseline to Week 4 and Month 18-24

• Total Daily Dose of Chronocort in mg/Day/m^2 of Hydrocortisone by BSA During the Time Interval Baseline to Week 4 and Month 18 to Month 24

  Baseline to Week 4 and Month 18-24

• Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP)

  Baseline and Week 24

• Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4)

  Baseline and Week 24

• Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin

  Baseline, Month 24

Study Arms (1)

Chronocort®

EXPERIMENTAL

Chronocort® modified release hydrocortisone

Drug: Hydrocortisone

Interventions

Hydrocortisone DRUG

Modified release hydrocortisone

Chronocort®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with CAH who have successfully completed a clinical trial with the current formulation of Chronocort®.
• Provision of signed written informed consent.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Neurocrine UK Limited: lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892-1932, United States

Location

Related Publications (1)

• Merke DP, Mallappa A, Arlt W, Brac de la Perriere A, Linden Hirschberg A, Juul A, Newell-Price J, Perry CG, Prete A, Rees DA, Reisch N, Stikkelbroeck N, Touraine P, Maltby K, Treasure FP, Porter J, Ross RJ. Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2063-e2077. doi: 10.1210/clinem/dgab051.

  PMID: 33527139 DERIVED

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Clinical Trials Information
• Organization: Diurnal Limited

info@diurnal.co.uk

+44 (0) 292 068 2069

Study Officials

• Principal Investigator

  Neurocrine UK Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: February 23, 2017
• Study Start: August 18, 2016
• Primary Completion: July 13, 2022
• Study Completion: July 13, 2022
• Last Updated: October 28, 2024
• Results First Posted: October 24, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)