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

Brief Title

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

Official Title

An Open-label, Randomized, Titration-blinded, Phase III Study of Efficacy, Safety and Tolerability Of Chronocort® Compared With Standard Glucocorticoid REeplacement Therapy in the Treatment of Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia

Brief Summary

      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.
    

Detailed 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).
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Non-inferiority of Chronocort® versus standard care in terms of responder rate.

Secondary Outcome

 Impact of both treatments on markers of fertility.

Condition

Congenital Adrenal Hyperplasia

Intervention

Chronocort®

Study Arms / Comparison Groups

 Chronocort
Description:  Hydrocortisone modified release capsules - Chronocort®. 66 subjects will be randomised to this group using an interactive web response system (IWRS).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

October 4, 2018

Completion Date

July 9, 2021

Primary Completion Date

October 17, 2018

Eligibility Criteria

        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.
      

Gender

All

Ages

16 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03532022

Organization ID

DIUR-007


Responsible Party

Sponsor

Study Sponsor

Diurnal Limited

Collaborators

 National Institutes of Health (NIH)

Study Sponsor

, , 


Verification Date

March 2022