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Open-label Comparison of Chronocort® Versus Standard Glucocorticoid Replacement Therapy (RESTORE)

D

Diurnal

Status and phase

Withdrawn
Phase 3

Conditions

Congenital Adrenal Hyperplasia

Treatments

Drug: Standard Care
Drug: Chronocort®

Study type

Interventional

Funder types

Industry
NIH

Identifiers

NCT03532022
DIUR-007

Details and patient eligibility

About

This study is an open-label, randomised, titration-blinded, parallel arm, multicenter study to compare twice daily Chronocort® with standard care in participants with Congenital Adrenal Hyperplasia (CAH). This study will be conducted in the USA.

Full description

It will compare the efficacy, safety and tolerability of twice daily Chronocort® with standard care (using the participant's usual individualized standard glucocorticoid regimen) over a treatment period of 52 weeks in participants aged 16 years and over with known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-OHP or A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids).

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply (note: if a participant fails to meet an inclusion criterion, re-screening is permitted if the Investigator considers that the circumstances leading to screening failure will not be relevant when the participant is re-screened at a later time):

Age

  1. Participant must be aged 16 years or older at the time of signing the informed consent.

  2. In participants aged <18 years, height velocity must be less than 2 cm in the last year and puberty must be completed.

    Type of Participant and Disease Characteristics

  3. Participants with known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-OHP or A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids).

    Sex

  4. Male and female participants

    1. Male participants:

      • A male participant must agree to use contraception as detailed in Section 10.4 of this protocol during the treatment period and refrain from donating sperm during this period.
    2. Female participants:

      • A female participant is eligible to participate if she is not pregnant (Section 10.4), not breastfeeding, and at least one of the following conditions applies:

    i. Not a woman of childbearing potential (WOCBP) as defined in Section 10.4. OR ii. A WOCBP with a negative pregnancy test at entry into the study who agrees to follow the contraceptive guidance in Section 10.4 during the treatment period.

    Note: females presenting with oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially fertile and therefore, as well as undergoing pregnancy testing like all other female participants, will be expected to be using an acceptable method of contraception which should have been ongoing for ≥90 days prior to the study.

    Informed Consent

  5. Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply (note: if a participant meets an exclusion criterion, re-screening is permitted if the Investigator considers that the circumstances leading to screening failure will not be relevant when the participant is re-screened at a later time):

Medical Conditions

  1. Clinical or biochemical evidence of hepatic or renal disease e.g. creatinine > 2 times the upper limit of normal (ULN) or elevated liver function tests (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >2 times the ULN).

  2. History of bilateral adrenalectomy.

  3. History of malignancy (other than basal cell carcinoma successfully treated >26 weeks prior to entry into the study).

  4. Participants who have type 1 diabetes or any participant who is receiving insulin.

  5. Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.

    Prior/Concomitant Therapy

  6. Participants on regular daily oral steroids for any indication other than CAH. Note: a participant should not be given any steroids (even on an irregular basis) within 5 days of a study visit. If there is a medical need for steroid treatment within this time frame then the visit should be postponed until a 5-day interval has elapsed.

  7. Co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids (examples provided at http://medicine.iupui.edu/clinpharm/ddis/clinical-table/).

  8. Participants who are receiving <10 mg hydrocortisone dose at baseline or the hydrocortisone dose equivalent.

    Prior/Concurrent Clinical Study Experience

  9. Participation in another clinical study of an investigational or licensed drug or device within the 12 weeks prior to screening or during the study.

  10. Inclusion in any natural history or translational research study that would require evaluation of androgen levels during the study period outside of this study protocol assessments.

  11. Participants who have previously been exposed to Chronocort in studies DIUR-003, DIUR-005 or DIUR-006.

    Other Exclusions

  12. Participants who routinely work night shifts and so do not sleep during the usual night-time hours.

  13. Participants unable to comply with the requirements of the protocol.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

0 participants in 2 patient groups

Chronocort
Experimental group
Description:
Hydrocortisone modified release capsules - Chronocort®. 66 subjects will be randomised to this group using an interactive web response system (IWRS).
Treatment:
Drug: Chronocort®
Standard Care
Active Comparator group
Description:
Subjects participating in this arm will continue to receive their normal, standard care (hydrocortisone, dexamethasone, prednisone, prednisolone) once enrolled on the study. 66 subjects will be randomised to this arm using an interactive web response system (IWRS).
Treatment:
Drug: Standard Care

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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