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CompletedNCT05063994CONnECTUpdated Feb 25, 2025Results posted

Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia

A Phase 3 interventional study of Chronocort and Cortef in Congenital Adrenal Hyperplasia, sponsored by Neurocrine UK Limited. Completed at 21 sites in 3 countries. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2025-02-25.

Sponsored by Neurocrine UK Limited · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
55
Allocation
Randomized
Ages
16 Years and older
Sex
All
01

Study summary

This study is a randomized, double-blind, active-controlled, phase III study of Chronocort® compared with immediate-release hydrocortisone replacement therapy in participants aged 16 years and over with Congenital Adrenal Hyperplasia.

Read the detailed description

The study will compare the efficacy, safety and tolerability of twice daily Chronocort with twice daily immediate release hydrocortisone replacement therapy (IRHC) (Cortef®) in participants aged 16 years and over with known classic Congenital Adrenal Hyperplasia (CAH) due to 21 hydroxylase deficiency.

02

Conditions studied

  • Congenital Adrenal Hyperplasia
03

Who can participate

Ages eligible
16 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male or female participants must be aged 16 years or older at the time of signing the informed consent/assent.
  • In participants aged \<18 years, height velocity must be less than 2 cm/year in the last year and puberty must be completed (Tanner stage V).
  • Participants with known classic CAH due to 21 hydroxylase deficiency diagnosed in childhood with documented (at any time) elevated 17-OHP and with or without elevated A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids) and on stable glucocorticoid therapy for a minimum of 3 months.
  • Participants who are receiving fludrocortisone must be on a documented stable dose for a minimum of 3 months prior to enrollment and must have stable renin levels at screening.
  • Female participants of childbearing potential and all male participants must agree to the use of an accepted method of contraception during the study.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and she is either not a woman of childbearing potential (WOCBP) or has a negative pregnancy test at entry into the study. Note: females presenting with oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially fertile and therefore should undergo pregnancy testing like all other female participants.
  • Capable of giving signed informed consent/assent which includes compliance with requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria

Exclusion Criteria:

  • 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).
  • History of bilateral adrenalectomy.
  • History of malignancy (other than basal cell carcinoma successfully treated >26 weeks prior to entry into the study).
  • Participants who have type 1 diabetes or receive regular insulin, have uncontrolled diabetes, or have a screening HbA1c greater than 8%.
  • Persistent signs of adrenal insufficiency or the participant does not tolerate treatment at the end of the 4-week run-in period.
  • Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.
  • Participants on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
  • Co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids.
  • Participants who are receiving \<10 mg hydrocortisone dose at screening or the hydrocortisone dose equivalent.
  • Participants anticipating regular prophylactic use of additional steroids e.g. for strenuous exercise.
  • Participation in another clinical study of an investigational or licensed drug or device within the 12 weeks prior to screening.
  • Inclusion in any natural history or translational research study that would require evaluation of androgen levels during the study period outside of this protocol's assessments.
  • Participants who have previously been exposed to Chronocort in any Diurnal study.
  • Participants who routinely work night shifts and so do not sleep during the usual night-time hours.
  • Participants, who in the opinion of the Investigator, will be unable to comply with the requirements of the protocol.
  • Participants with a known hypersensitivity to any of the components of the Chronocort capsules, the Cortef tablets, or the placebo capsules.
  • Participants with congenital galactosemia, malabsorption of glucose and galactose, or who are lactase deficient.
  • Participants with a body weight of 45 kg or less.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
55 participants (actual)

Study arms

  • Experimental
    Chronocort

    Participants received Chronocort at a starting dose of 30 milligrams (mg), with dose adjustments down to 25, 20, or 15 mg based on adrenal insufficiency symptoms and androgen levels. Placebo was used for dose adjustment to maintain blinding.

    Drug: Chronocort · Other: Placebo

  • Active comparator
    Cortef

    Participants received Cortef at a starting dose of 30 mg, with dose adjustments down to 25, 20, or 15 mg based on adrenal insufficiency symptoms and androgen levels. Placebo was used for dose adjustment to maintain blinding.

    Drug: Cortef · Other: Placebo

Interventions

  • DrugChronocort

    Over-encapsulated hydrocortisone modified-release capsule for oral administration.

    Also known as: Hydrocortisone modified-release

  • DrugCortef

    Over-encapsulated hydrocortisone immediate-release tablet for oral administration.

    Also known as: Immediate-release hydrocortisone, IRHC

  • OtherPlacebo

    Matching placebo

05

What researchers measure

Primary outcomes

  1. Percentage of Participants Who Were Biochemical Responders at Week 28

    Biochemical response was defined as a participant who a) was in biochemical control at the 08:00 assessment and b) was receiving a total daily dose of hydrocortisone of not more than 25 mg if the participant was in biochemical control at baseline or not more than 30 mg if the participant was not in biochemical control at baseline. Biochemical control was defined as both a 17-OHP concentration equal to or below the upper limit for optimal control (1200 ng/dL \[36.4 nmol/L\]) and an A4 concentration equal to or below the upper limit of the reference range (150 ng/dL \[5.2 nmol/L\] for men and 200 ng/dL \[7.0 nmol/L\] for women). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Week 28

Secondary outcomes

  1. Percentage of Participants Who Were Dose Responders at Week 28

    Dose response was defined as a participant who a) was receiving a total daily dose of hydrocortisone of not more than 25 mg and b) was in biochemical control at the 08:00 assessment. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Week 28

  2. Total Daily Dose of Hydrocortisone at Week 28

    Least squares (LS) mean was assessed using mixed model repeated measures (MMRM). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Week 28

  3. Number of Participants in Biochemical Control

    Biochemical control was defined as both a 17-OHP concentration (assessed at 08:00) equal to or below the upper limit for optimal control (1200 ng/dL \[36.4 nmol/L\]) and an A4 concentration equal to or below the upper limit of the reference range (150 ng/dL \[5.2 nmol/L\] for men and 200 ng/dL \[7.0 nmol/L\] for women). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline and Week 28

  4. Change From Baseline in Mean of 08:00 and 13:00 17-OHP Levels at Week 28

    LS mean was assessed using analysis of covariance (ANCOVA). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  5. Change From Baseline in Mean of 08:00 and 13:00 A4 Levels at Week 28

    LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  6. Number of Participants With Menstrual Regularity (Females of Childbearing Potential Only) at Week 28

    Data are presented for the number of participants with more than monthly menstrual cycles, monthly menstrual cycles, and number of participants with oligomenorrhoea and amenorrhoea. Oligomenorrhoea was defined as fewer than 9 menstrual cycles per year or cycle length \>35 days and amenorrhoea as absent menses for ≥ 3 months. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Week 28

  7. Change From Baseline in Luteinizing Hormone Levels (Males Only) at Week 28

    LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  8. Percent Change From Baseline in Size of Testicular Adrenal Rest Tumors at Week 28 (Males Only)

    Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Week 28

  9. Change From Baseline in Hirsutism at Week 28 Using the Ferriman-Gallwey Score (Females Only) at Week 28

    Ferriman-Gallwey score is a method used to assess and quantify hirsutism in women. A total score \< 8 is considered normal whereas a score of 8 to 15 indicates mild hirsutism. A score \>15 indicates moderate or severe hirsutism. The Ferriman-Gallwey score ranged from 0 to 36. Higher score indicated more hirsutism. Change from baseline is reported (negative change from baseline indicated improvement). LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  10. Change From Baseline in Acne Using the Global Evaluation Acne (GEA) Scale (Females Only) at Week 28

    Acne severity was assessed according to GEA scale, which ranged from 0 (Clear. No lesions) to 5 (Very severe). Higher score indicated higher severity of acne. Change from baseline is reported (negative change from baseline indicated improvement). LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  11. Change From Baseline in Glycated Hemoglobin (HbA1c) Percent Levels at Week 28

    LS mean was assessed by ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  12. Change From Baseline in Waist Circumference at Week 28

    LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  13. Change From Baseline in Body Weight at Week 28

    LS mean was assessed by ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

  14. Change From Baseline Quality of Life Using the Self-completed Medical Outcome Study 36-Item Short Form Health Survey (SF-36) Total Score for the Physical and Mental Components and the Sub-domain of Vitality at Week 28

    SF-36 evaluates aspects of functional health and well-being. The physical component has 4 sub-scales: physical function, role limitations due to physical problems, pain, and general health perception; and the mental component has 4 sub-scales: vitality, social function, role limitations due to emotional problems, and mental health. Total scores for the physical and mental component are presented as well as the sub-scale score for vitality. Scores were summarized and transformed into a range from 0 to 100; 0=worst, and 100=best outcome. Higher scores indicated better outcome. Change from baseline is reported (positive change from baseline indicated improvement). LS mean was assessed by ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

    Time frame: Baseline, Week 28

06

Results

Posted Feb 24, 2025

Participant flow

Cortef Run-In
Participant flow — Cortef Run-In
MilestoneCortef Run-InChronocortCortef
Started5500
Completed5300
Not completed200
Withdrew: Withdrawal of consent100
Withdrew: Did not meet the inclusion/exclusion criteria at end of run-in100
Treatment
Participant flow — Treatment
MilestoneCortef Run-InChronocortCortef
Started02528
Full analysis set (fas) population02528
Completed02525
Not completed003
Withdrew: Physician decision001
Withdrew: Withdrawal by subject001
Withdrew: Withdrawal of consent001

Outcome measures

PrimaryPercentage of Participants Who Were Biochemical Responders at Week 28

Biochemical response was defined as a participant who a) was in biochemical control at the 08:00 assessment and b) was receiving a total daily dose of hydrocortisone of not more than 25 mg if the participant was in biochemical control at baseline or not more than 30 mg if the participant was not in biochemical control at baseline. Biochemical control was defined as both a 17-OHP concentration equal to or below the upper limit for optimal control (1200 ng/dL \[36.4 nmol/L\]) and an A4 concentration equal to or below the upper limit of the reference range (150 ng/dL \[5.2 nmol/L\] for men and 200 ng/dL \[7.0 nmol/L\] for women). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Week 28
Reported as:
Number · percentage of participants
Percentage of Participants Who Were Biochemical Responders at Week 28
percentage of participantsChronocortCortef
Percentage of Participants Who Were Biochemical Responders at Week 2840.014.3
Statistical analysis
  • Chronocort vs Cortef · Regression, Logistic · p = 0.0003 (One-sided non-inferiority. The Ge et al (2011) method was used to calculate the estimate, standard error, confidence interval and P-value for the treatment difference from the results of a logistic regression analysis.) · Treatment difference: 25.7 · 95% CI 2.5 to 48.9
SecondaryPercentage of Participants Who Were Dose Responders at Week 28

Dose response was defined as a participant who a) was receiving a total daily dose of hydrocortisone of not more than 25 mg and b) was in biochemical control at the 08:00 assessment. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Week 28
Reported as:
Number · percentage of participants
Percentage of Participants Who Were Dose Responders at Week 28
percentage of participantsChronocortCortef
Percentage of Participants Who Were Dose Responders at Week 2836.010.7
Statistical analysis
  • Chronocort vs Cortef · Regression, Logistic · p = 0.012 (One-sided superiority. The Ge et al (2011) method was used to calculate the estimate, standard error, confidence interval and P-value for the treatment difference from the results of a logistic regression analysis.) · Treatment difference: 25.3 · 95% CI 3.3 to 47.3
SecondaryTotal Daily Dose of Hydrocortisone at Week 28

Least squares (LS) mean was assessed using mixed model repeated measures (MMRM). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Week 28
Reported as:
Least squares mean · mg
Total Daily Dose of Hydrocortisone at Week 28
mgChronocortCortef
Total Daily Dose of Hydrocortisone at Week 2820.2 (17.8 to 22.6)26.0 (23.7 to 28.3)
Statistical analysis
  • Chronocort vs Cortef · MMRM · p = 0.0005 (One-sided superiority.) · Treatment difference: -5.8 · 95% CI -9.2 to -2.5
SecondaryNumber of Participants in Biochemical Control

Biochemical control was defined as both a 17-OHP concentration (assessed at 08:00) equal to or below the upper limit for optimal control (1200 ng/dL \[36.4 nmol/L\]) and an A4 concentration equal to or below the upper limit of the reference range (150 ng/dL \[5.2 nmol/L\] for men and 200 ng/dL \[7.0 nmol/L\] for women). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline and Week 28
Reported as:
Count of participants · Participants
Number of Participants in Biochemical Control
ParticipantsChronocortCortef
Baseline138
Week 28104
SecondaryChange From Baseline in Mean of 08:00 and 13:00 17-OHP Levels at Week 28

LS mean was assessed using analysis of covariance (ANCOVA). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · ng/dL
Change From Baseline in Mean of 08:00 and 13:00 17-OHP Levels at Week 28
ng/dLChronocortCortef
Change From Baseline in Mean of 08:00 and 13:00 17-OHP Levels at Week 28-1223.91 (-2897.42 to 449.6)1612.17 (-61.34 to 3285.68)
SecondaryChange From Baseline in Mean of 08:00 and 13:00 A4 Levels at Week 28

LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · ng/dL
Change From Baseline in Mean of 08:00 and 13:00 A4 Levels at Week 28
ng/dLChronocortCortef
Change From Baseline in Mean of 08:00 and 13:00 A4 Levels at Week 28-4.85 (-115.57 to 105.86)146.13 (35.42 to 256.85)
SecondaryNumber of Participants With Menstrual Regularity (Females of Childbearing Potential Only) at Week 28

Data are presented for the number of participants with more than monthly menstrual cycles, monthly menstrual cycles, and number of participants with oligomenorrhoea and amenorrhoea. Oligomenorrhoea was defined as fewer than 9 menstrual cycles per year or cycle length \>35 days and amenorrhoea as absent menses for ≥ 3 months. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Week 28
Reported as:
Count of participants · Participants
Number of Participants With Menstrual Regularity (Females of Childbearing Potential Only) at Week 28
ParticipantsChronocortCortef
More than Monthly00
Monthly92
Oligomenorrhoea24
Amenorrhoea36
SecondaryChange From Baseline in Luteinizing Hormone Levels (Males Only) at Week 28

LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · mIU/mL
Change From Baseline in Luteinizing Hormone Levels (Males Only) at Week 28
mIU/mLChronocortCortef
Change From Baseline in Luteinizing Hormone Levels (Males Only) at Week 280.15 (-0.71 to 1.02)-1.19 (-2.01 to -0.37)
SecondaryPercent Change From Baseline in Size of Testicular Adrenal Rest Tumors at Week 28 (Males Only)

Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Week 28
Reported as:
Mean · percent change
Percent Change From Baseline in Size of Testicular Adrenal Rest Tumors at Week 28 (Males Only)
percent changeChronocortCortef
Percent Change From Baseline in Size of Testicular Adrenal Rest Tumors at Week 28 (Males Only)-7.67 ± 9.220-0.90 ± 1.810
SecondaryChange From Baseline in Hirsutism at Week 28 Using the Ferriman-Gallwey Score (Females Only) at Week 28

Ferriman-Gallwey score is a method used to assess and quantify hirsutism in women. A total score \< 8 is considered normal whereas a score of 8 to 15 indicates mild hirsutism. A score \>15 indicates moderate or severe hirsutism. The Ferriman-Gallwey score ranged from 0 to 36. Higher score indicated more hirsutism. Change from baseline is reported (negative change from baseline indicated improvement). LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · score on a scale
Change From Baseline in Hirsutism at Week 28 Using the Ferriman-Gallwey Score (Females Only) at Week 28
score on a scaleChronocortCortef
Change From Baseline in Hirsutism at Week 28 Using the Ferriman-Gallwey Score (Females Only) at Week 28-1.0 (-2.5 to 0.6)-1.2 (-3.0 to 0.5)
SecondaryChange From Baseline in Acne Using the Global Evaluation Acne (GEA) Scale (Females Only) at Week 28

Acne severity was assessed according to GEA scale, which ranged from 0 (Clear. No lesions) to 5 (Very severe). Higher score indicated higher severity of acne. Change from baseline is reported (negative change from baseline indicated improvement). LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · score on a scale
Change From Baseline in Acne Using the Global Evaluation Acne (GEA) Scale (Females Only) at Week 28
score on a scaleChronocortCortef
Change From Baseline in Acne Using the Global Evaluation Acne (GEA) Scale (Females Only) at Week 28-0.3 (-0.5 to -0.1)-0.2 (-0.4 to 0.0)
SecondaryChange From Baseline in Glycated Hemoglobin (HbA1c) Percent Levels at Week 28

LS mean was assessed by ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · percent HbA1c
Change From Baseline in Glycated Hemoglobin (HbA1c) Percent Levels at Week 28
percent HbA1cChronocortCortef
Change From Baseline in Glycated Hemoglobin (HbA1c) Percent Levels at Week 28-0.01 (-0.09 to 0.06)-0.06 (-0.13 to 0.01)
SecondaryChange From Baseline in Waist Circumference at Week 28

LS mean was assessed using ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · centimeters
Change From Baseline in Waist Circumference at Week 28
centimetersChronocortCortef
Change From Baseline in Waist Circumference at Week 280.867 (-1.387 to 3.121)-1.242 (-3.496 to 1.012)
SecondaryChange From Baseline in Body Weight at Week 28

LS mean was assessed by ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · kilograms
Change From Baseline in Body Weight at Week 28
kilogramsChronocortCortef
Change From Baseline in Body Weight at Week 281.29 (0.00 to 2.58)-1.67 (-2.96 to -0.38)
SecondaryChange From Baseline Quality of Life Using the Self-completed Medical Outcome Study 36-Item Short Form Health Survey (SF-36) Total Score for the Physical and Mental Components and the Sub-domain of Vitality at Week 28

SF-36 evaluates aspects of functional health and well-being. The physical component has 4 sub-scales: physical function, role limitations due to physical problems, pain, and general health perception; and the mental component has 4 sub-scales: vitality, social function, role limitations due to emotional problems, and mental health. Total scores for the physical and mental component are presented as well as the sub-scale score for vitality. Scores were summarized and transformed into a range from 0 to 100; 0=worst, and 100=best outcome. Higher scores indicated better outcome. Change from baseline is reported (positive change from baseline indicated improvement). LS mean was assessed by ANCOVA. Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

Time frame:
Baseline, Week 28
Reported as:
Least squares mean · score on a scale
Change From Baseline Quality of Life Using the Self-completed Medical Outcome Study 36-Item Short Form Health Survey (SF-36) Total Score for the Physical and Mental Components and the Sub-domain of Vitality at Week 28
score on a scaleChronocortCortef
Physical Component-3.313 (-5.801 to -0.824)-1.031 (-3.976 to 1.913)
Mental Component0.772 (-3.209 to 4.752)0.685 (-4.034 to 5.403)
Vitality Sub-domain-0.847 (-4.354 to 2.660)-0.002 (-4.157 to 4.153)

Adverse events

Collected over Up to 30 days after last study dose (maximum treatment duration of approximately 53 weeks; median exposure = 255.0 days for Chronocort and 230.5 days for Cortef). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cortef Run-In0/55 (0%)0/55 (0%)2/55 (3.6%)
Chronocort0/25 (0%)2/25 (8%)22/25 (88%)
Cortef0/28 (0%)1/28 (3.6%)24/28 (85.7%)
Most frequent serious events
Most frequent serious events
EventCortef Run-InChronocortCortef
COVID-19Infections and infestations0/551/250/28
Malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/551/250/28
PneumoniaRespiratory, thoracic and mediastinal disorders0/550/251/28
Most frequent other events
Showing 10 of 19
Most frequent other events
EventCortef Run-InChronocortCortef
PyrexiaGeneral disorders0/550/256/28
FatigueGeneral disorders0/554/255/28
HeadacheNervous system disorders0/554/253/28
Weight increasedInvestigations0/553/250/28
ArthralgiaMusculoskeletal and connective tissue disorders0/553/252/28
Blood creatine phosphokinase increasedInvestigations0/551/253/28
GastroenteritisInfections and infestations0/552/252/28
Ear infectionInfections and infestations0/552/250/28
SinusitisInfections and infestations0/552/251/28
Ligament sprainInjury, poisoning and procedural complications0/552/250/28

Baseline characteristics

FAS: All participants with congenital adrenal hyperplasia (CAH) who were randomized into the study and who received at least 1 dose of study drug.

Age, Continuous
Age, Continuous(years)ChronocortCortefTotal
Mean36.7 ± 14.6831.6 ± 13.0234.0 ± 13.93
Sex: Female, Male
Sex: Female, Male(Participants)ChronocortCortefTotal
Female161632
Male91221
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)ChronocortCortefTotal
Hispanic or Latino235
Not Hispanic or Latino151631
Unknown or Not Reported8917
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)ChronocortCortefTotal
White131225
Black or African American123
Asian459
Not Reportable6612
Unknown134
17-Hydroxyprogesterone (17-OHP) Level
17-Hydroxyprogesterone (17-OHP) Level(nanograms (ng)/deciliters (dL))ChronocortCortefTotal
Mean3470.48 (43.5 to 16968.5)5595.36 (10.0 to 14641.5)4593.06 (10.0 to 16968.5)
Androstenedione (A4) Level
Androstenedione (A4) Level(ng/dL)ChronocortCortefTotal
Mean173.30 (5.0 to 1040.5)483.09 (5.0 to 2516.5)334.15 (5.0 to 2516.5)
07

Study locations

21 sites
  • Diurnal Investigational Site in Los Angeles
    Los Angeles, California 90027, United States
  • Diurnal Investigational Site in Orange
    Orange, California 92868, United States
  • Diurnal Investigational Site in Jacksonville
    Jacksonville, Florida 32207, United States
  • Diurnal Investigational Site in Iowa
    Iowa City, Iowa 52224, United States
  • Diurnal Investigational Site in Maryland
    Bethesda, Maryland 20892-1932, United States
  • Diurnal Investigational Site in Michigan
    Ann Arbor, Michigan 48109, United States
  • Diurnal Investigational Site in Rochester
    Rochester, Minnesota 55901, United States
  • Diurnal Investigational Site in Nevada
    Las Vegas, Nevada 89148, United States
  • Diurnal Investigational Site in Dallas
    Dallas, Texas 75235, United States
  • Diurnal Investigational Site in Seattle
    Seattle, Washington 98105, United States
  • Diurnal Investigational Site in Milwaukee
    Milwaukee, Wisconsin 53226, United States
  • Diurnal Investigational Site in Caen
    Caen, Normandy 14033, France
  • Diurnal Investigational Site in Pessac
    Bordeaux, 33604, France
  • Diurnal Investigational Site in Bron
    Lyon, 69677, France
  • Diurnal Investigational Site in Paris
    Paris, 75651, France
  • Diurnal Investigational Site in Toulouse (Children's Hospital)
    Toulouse, 31059, France
  • Diurnal Investigational Site in Toulouse
    Toulouse, 31059, France
  • Diurnal Investigational Site in Asahi-ku
    Yokohama-shi, Kanagawa 241-0811, Japan
  • Diurnal Investigational Site in Yushima
    Bunkyō-Ku, Tokyo 113-8519, Japan
  • Diurnal Investigational Site in Okura
    Setagaya-Ku, Tokyo 157-8535, Japan
  • Diurnal Investigational Site in Toyama
    Shinjuku-Ku, Tokyo 162-8655, Japan
08

References and documents

Study documents

  • Study protocol · Oct 30, 2023
  • Statistical analysis plan · Feb 22, 2024

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT05063994
Lead sponsor
Neurocrine UK Limited
Responsible party
Sponsor
First posted
Oct 1, 2021
Start date
May 24, 2022
Primary completion
Feb 2, 2024
Completion
Feb 2, 2024
Results posted
Feb 24, 2025
Last update
Feb 25, 2025

Study contacts

Principal Investigator
principal investigator · Neurocrine UK Limited

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.

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Discussion

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