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Trial record 21 of 107 for:    "21-hydroxylase deficiency"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02716818
Recruitment Status : Completed
First Posted : March 23, 2016
Results First Posted : September 4, 2019
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Diurnal Limited

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Congenital Adrenal Hyperplasia
Interventions Drug: Chronocort®
Drug: standard glucocorticoid therapy
Enrollment 122
Recruitment Details This study was conducted at 11 study sites in 7 countries: Denmark 1, France 2, Germany 1,Netherlands 1, Sweden 1, UK 4, and USA 1.
Pre-assignment Details Following written informed consent and screening tests (Visit 0), eligible participants were called back for the baseline visit. As part of the baseline assessment, participants were admitted overnight for a 24- hour endocrine profile whilst remaining on their standard therapy. Participants were then randomised to Chronocort or standard therapy.
Arm/Group Title Chronocort® Standard Glucocorticoid Therapy
Hide Arm/Group Description

Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subject's previous glucocorticoid therapy dose and then dose titrated to effect.

Chronocort®: Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.

Subjects in this arm will continue their previous oral glucocorticoid therapy, titrated to effect. Standard glucocorticoid therapy may consist of:

  1. Hydrocortisone only
  2. Prednisone or prednisolone, alone or in combination with hydrocortisone
  3. Dexamethasone, alone or in combination with any other glucocorticoid
Period Title: Overall Study
Started 61 61
Completed 58 59
Not Completed 3 2
Arm/Group Title Chronocort® Standard Glucocorticoid Therapy Total
Hide Arm/Group Description

Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subjects previous glucocorticoid therapy dose and then dose titrated to effect.

Chronocort®: Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.

Subjects in this arm will continue their previous oral glucocorticoid therapy, titrated to effect. Standard glucocorticoid therapy may consist of:

  1. Hydrocortisone only
  2. Prednisone or prednisolone, alone or in combination with hydrocortisone
  3. Dexamethasone, alone or in combination with any other glucocorticoid
Total of all reporting groups
Overall Number of Baseline Participants 61 61 122
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 61 participants 122 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
61
 100.0%
59
  96.7%
120
  98.4%
>=65 years
0
   0.0%
2
   3.3%
2
   1.6%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 61 participants 61 participants 122 participants
35.2
(19 to 61)
37.5
(19 to 68)
36.3
(19 to 68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 61 participants 122 participants
Female
42
  68.9%
36
  59.0%
78
  63.9%
Male
19
  31.1%
25
  41.0%
44
  36.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 61 participants 122 participants
White
60
  98.4%
60
  98.4%
120
  98.4%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Other - Antillean
1
   1.6%
0
   0.0%
1
   0.8%
Other - Palestinian
0
   0.0%
1
   1.6%
1
   0.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants 61 participants 122 participants
United States 4 4 8
Europe 57 57 114
1.Primary Outcome
Title Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for 17-OHP
Hide Description Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for 17-OHP (17-Hydroxyprogesterone). The primary efficacy variable was the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of 17-OHP. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed 17-OHP values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of 17-OHP when compared to baseline (0).
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy evaluable analysis set (EES) comprised all participants who were randomised into the study, who received at least one dose of Chronocort or standard GC therapy, and who had an evaluable Week 24 17-OHP 24-hour hormone profile, and who had no major protocol violations. Total sum of participants in the EES = 105.
Arm/Group Title Chronocort® Standard Glucocorticoid Therapy
Hide Arm/Group Description:

Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subjects previous glucocorticoid therapy dose and then dose titrated to effect.

Chronocort®: Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.

Subjects in this arm will continue their previous oral glucocorticoid therapy, titrated to effect. Standard glucocorticoid therapy may consist of:

  1. Hydrocortisone only
  2. Prednisone or prednisolone, alone or in combination with hydrocortisone
  3. Dexamethasone, alone or in combination with any other glucocorticoid
Overall Number of Participants Analyzed 53 52
Mean (Standard Deviation)
Unit of Measure: Z-score
-0.403  (0.8499) -0.172  (0.7776)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronocort®, Standard Glucocorticoid Therapy
Comments The primary efficacy variable was the natural logarithm of the mean of the 24-hour SDS profile for the natural logarithm of 17-OHP. The SDS profile was calculated as the SDS of log transformed 17-OHP concentration unsigned. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs, with the first and last (13th) weighted one half relative to the intermediate SDSs.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5521
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.069
Confidence Interval (2-Sided) 95%
-0.299 to 0.161
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for A4
Hide Description Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for A4 (androstenedione). This secondary efficacy variable was calculated as follows: the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of A4. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed A4 values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of A4 when compared to baseline (0).
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy evaluable analysis set (EES) comprised all participants who were randomised into the study, who received at least one dose of Chronocort or standard GC therapy, and who had an evaluable Week 24 17-OHP 24-hour hormone profile, and who had no major protocol violations. Total sum of participants in the EES = 105.
Arm/Group Title Chronocort® Standard Glucocorticoid Therapy
Hide Arm/Group Description:

Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subjects previous glucocorticoid therapy dose and then dose titrated to effect.

Chronocort®: Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.

Subjects in this arm will continue their previous oral glucocorticoid therapy, titrated to effect. Standard glucocorticoid therapy may consist of:

  1. Hydrocortisone only
  2. Prednisone or prednisolone, alone or in combination with hydrocortisone
  3. Dexamethasone, alone or in combination with any other glucocorticoid
Overall Number of Participants Analyzed 53 52
Mean (Standard Deviation)
Unit of Measure: Z-score
0.113  (0.9221) -0.041  (0.7731)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronocort®, Standard Glucocorticoid Therapy
Comments Change from Baseline to 24 Weeks in A4 Using an ANCOVA Model - The analysis conducted for the primary endpoint variable analysis of 17-OHP was repeated for A4.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.7405
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.047
Confidence Interval (2-Sided) 95%
-0.234 to 0.329
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 17-OHP and A4 by Individual Baseline Treatment Strata.
Hide Description 17-OHP and A4 by individual baseline treatment strata presented in the same manner as the primary endpoint (using 24-hour SDS profile at 24 weeks). Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for 17-OHP and A4. This secondary efficacy variable was calculated as follows: the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of 17-OHP and A4. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed 17-OHP and A4 values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of 17-OHP and A4 when compared to baseline (0).
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy evaluable analysis set (EES) comprised all participants who were randomised into the study, who received at least one dose of Chronocort or standard GC therapy, and who had an evaluable Week 24 17-OHP 24-hour hormone profile, and who had no major protocol violations. Total sum of participants in the EES = 105.
Arm/Group Title Pre-Baseline - Hydrocortisone - 17-OHP Pre-Baseline - Prednisone/Prednisolone - 17-OHP Pre-Baseline - Dexamethasone - 17-OHP Pre-Baseline - Chronocort vs. Hydrocortisone - 17-OHP Pre-Baseline - Chronocort vs. Prednisone/Prednisolone - 17-OHP Pre-Baseline - Chronocort vs. Dexamethasone - 17-OHP Pre-Baseline - Hydrocortisone - A4 Pre-Baseline - Prednisone/Prednisolone - A4 Pre-Baseline - Dexamethasone - A4 Pre-Baseline - Chronocort vs. Hydrocortisone - A4 Pre-Baseline - Chronocort vs. Prednisone/Prednisolone - A4 Pre-Baseline - Chronocort vs. Dexamethasone - A4
Hide Arm/Group Description:
Secondary efficacy analysis of 17-OHP by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set).
Secondary efficacy analysis of 17-OHP by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set).
Secondary efficacy analysis of 17-OHP by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set).
Secondary efficacy analysis of 17-OHP by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set).
Secondary efficacy analysis of 17-OHP by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set).
Secondary efficacy analysis of 17-OHP by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set).
Secondary efficacy analysis of A4 by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set)
Secondary efficacy analysis of A4 by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set)
Secondary efficacy analysis of A4 by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set)
Secondary efficacy analysis of A4 by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set)
Secondary efficacy analysis of A4 by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set)
Secondary efficacy analysis of A4 by pre-treatment strata, change from baseline to 24 weeks in primary efficacy variable, analysis of covariance model (Efficacy evaluable analysis set)
Overall Number of Participants Analyzed 27 21 4 31 18 4 27 21 4 31 18 4
Mean (Standard Deviation)
Unit of Measure: Z-score
-0.248  (0.7661) -0.061  (0.8051) -0.245  (0.8522) -0.431  (0.8727) -0.320  (0.7627) -0.565  (1.2343) -0.211  (0.7426) 0.100  (0.8339) 0.368  (0.3521) 0.015  (1.0128) 0.328  (0.7256) -0.092  (1.0310)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pre-Baseline - Hydrocortisone - 17-OHP, Pre-Baseline - Chronocort vs. Hydrocortisone - 17-OHP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.8186
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.037
Confidence Interval (2-Sided) 95%
-0.354 to 0.281
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pre-Baseline - Prednisone/Prednisolone - 17-OHP, Pre-Baseline - Chronocort vs. Prednisone/Prednisolone - 17-OHP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.4655
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.135
Confidence Interval (2-Sided) 95%
-0.508 to 0.237
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pre-Baseline - Dexamethasone - 17-OHP, Pre-Baseline - Chronocort vs. Dexamethasone - 17-OHP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.9081
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.065
Confidence Interval (2-Sided) 95%
-1.32 to 1.451
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pre-Baseline - Hydrocortisone - A4, Pre-Baseline - Chronocort vs. Hydrocortisone - A4
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6729
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.092
Confidence Interval (2-Sided) 95%
-0.343 to 0.527
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pre-Baseline - Prednisone/Prednisolone - A4, Pre-Baseline - Chronocort vs. Prednisone/Prednisolone - A4
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5322
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.116
Confidence Interval (2-Sided) 95%
-0.257 to 0.489
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pre-Baseline - Dexamethasone - A4, Pre-Baseline - Chronocort vs. Dexamethasone - A4
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2885
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.568
Confidence Interval (2-Sided) 95%
-1.799 to 0.662
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With 17-OHP and A4 Levels in the Optimal Range at 9:00 at Week 24 Visit
Hide Description

17-OHP and A4 levels at 09:00 at the week 24 visit, as a responder analysis (i.e. the number of participants achieving results in the optimal range).

Optimal range for 17-OHP (male) = 1.2* - 6.7 nmol/L (female) = 1.2* - 8.6 Optimal range for A4 (male) = 1.4 - 5.2 nmol/L (female) = 1.0 - 7.0 nmol/L

* = There is no lower reference range available for 17-OHP, hence the lower limit of the optimal range was used in the derivation of the average Standard Deviation Score. This enabled calculation of an ‘unsigned’ SDS score which was used to assess potential over-treatment as well as under-treatment.

Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy evaluable analysis set (EES) comprised all participants who were randomised into the study, who received at least one dose of Chronocort or standard GC therapy, and who had an evaluable Week 24 17-OHP 24-hour hormone profile, and who had no major protocol violations. Total sum of participants in the EES = 105.
Arm/Group Title Chronocort - 09:00h Response - 17-OHP Chronocort - 09:00h Response - A4 Standard Glucocorticoid Therapy - 09:00h Response - 17-OHP Standard Glucocorticoid Therapy - 09:00h Response - A4
Hide Arm/Group Description:
Number of participants in the Chronocort arm (from the efficacy evaluable analysis set) achieving 17-OHP levels within the optimal range expected at 09:00h at the week 24 visit.
Number of participants in the Chronocort arm (from the efficacy evaluable analysis set) achieving A4 levels within the optimal range expected at 09:00h at the week 24 visit.
Number of participants in the standard glucocorticoid arm (from the efficacy evaluable analysis set) achieving 17-OHP levels within the optimal range expected at 09:00h at the week 24 visit.
Number of participants in the standard glucocorticoid arm (from the efficacy evaluable analysis set) achieving A4 levels within the optimal range expected at 09:00h at the week 24 visit.
Overall Number of Participants Analyzed 53 53 52 52
Measure Type: Count of Participants
Unit of Measure: Participants
30
  56.6%
25
  47.2%
30
  57.7%
30
  57.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronocort - 09:00h Response - 17-OHP, Standard Glucocorticoid Therapy - 09:00h Response - 17-OHP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.9877
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.45 to 2.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Chronocort - 09:00h Response - A4, Standard Glucocorticoid Therapy - 09:00h Response - A4
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.8498
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.43 to 2.02
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Fat Mass and Lean Mass)
Hide Description Changes relative to Standard glucocorticoid therapy in body composition (DEXA) (fat mass and lean mass) - measured at all sites except Germany.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy evaluable analysis set (EES) comprised all participants who were randomised into the study, who received at least one dose of Chronocort or standard GC therapy, and who had an evaluable Week 24 17-OHP 24-hour hormone profile, and who had no major protocol violations. German subjects were excluded from this analysis subset.
Arm/Group Title Chronocort - DEXA - Fat Mass Standard Glucocorticoid Therapy - DEXA - Fat Mass Chronocort - DEXA - Lean Mass Standard Glucocorticoid Therapy - DEXA - Lean Mass
Hide Arm/Group Description:
German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
Overall Number of Participants Analyzed 43 39 43 39
Mean (Standard Deviation)
Unit of Measure: kilograms
-0.575  (3.2744) 0.445  (2.4660) 0.640  (2.3304) 0.234  (1.3689)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronocort - DEXA - Fat Mass, Standard Glucocorticoid Therapy - DEXA - Fat Mass
Comments German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.156
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.96
Confidence Interval (2-Sided) 95%
-2.294 to 0.374
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Chronocort - DEXA - Lean Mass, Standard Glucocorticoid Therapy - DEXA - Lean Mass
Comments German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3392
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.425
Confidence Interval (2-Sided) 95%
-0.455 to 1.305
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Bone Mineral Density) - Measured at All Sites Except Germany.
Hide Description Changes relative to Standard glucocorticoid therapy in body composition (DEXA - bone mineral density only) - measured at all sites except Germany.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy evaluable analysis set (EES) comprised all participants who were randomised into the study, who received at least one dose of Chronocort or standard GC therapy, and who had an evaluable Week 24 17-OHP 24-hour hormone profile, and who had no major protocol violations. German subjects were excluded from this analysis subset.
Arm/Group Title Chronocort - DEXA - Bone Mineral Density Standard Glucocorticoid Therapy - DEXA - Bone Mineral Density
Hide Arm/Group Description:
German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
German subjects have been excluded from this analysis group as DEXA scans are not performed at German sites.
Overall Number of Participants Analyzed 35 36
Mean (Standard Deviation)
Unit of Measure: g/cm^2
-0.001  (0.0250) -0.008  (0.0399)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chronocort - DEXA - Bone Mineral Density, Standard Glucocorticoid Therapy - DEXA - Bone Mineral Density
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2614
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.009
Confidence Interval (2-Sided) 95%
-0.007 to 0.025
Estimation Comments [Not Specified]
Time Frame Adverse event information was collected from the point of enrolment to completion of the study (6 months).
Adverse Event Reporting Description Adverse event information was collected at each visit by the investigator and reported accordingly.
 
Arm/Group Title Chronocort® Standard Glucocorticoid Therapy
Hide Arm/Group Description

Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subjects previous glucocorticoid therapy dose and then dose titrated to effect.

Chronocort®: Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.

Subjects in this arm will continue their previous oral glucocorticoid therapy, titrated to effect. Standard glucocorticoid therapy may consist of:

  1. Hydrocortisone only
  2. Prednisone or prednisolone, alone or in combination with hydrocortisone
  3. Dexamethasone, alone or in combination with any other glucocorticoid
All-Cause Mortality
Chronocort® Standard Glucocorticoid Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   0/61 (0.00%)      0/61 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Chronocort® Standard Glucocorticoid Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/61 (11.48%)      5/61 (8.20%)    
Endocrine disorders     
Adrenocortical Insufficiency (acute)  1  0/61 (0.00%)  0 3/61 (4.92%)  3
Adrenal Insufficiency  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Gastrointestinal disorders     
Diarrhoea  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Vomiting  1  0/61 (0.00%)  0 1/61 (1.64%)  1
General disorders     
Oedema Peripheral  1  0/61 (0.00%)  0 1/61 (1.64%)  2
Pyrexia  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Infections and infestations     
Gastroenteritis * 1  2/61 (3.28%)  2 1/61 (1.64%)  1
Gastroenteritis Viral  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Appendicitis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Salpingitis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Tonsilitis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Diverticulitis  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Herpes Zoster  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/61 (0.00%)  0 1/61 (1.64%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Chronocort® Standard Glucocorticoid Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   59/61 (96.72%)      48/61 (78.69%)    
Blood and lymphatic system disorders     
Anaemia  1  4/61 (6.56%)  4 3/61 (4.92%)  3
Iron Deficiency Anaemia  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Cardiac disorders     
Palpitations  1  1/61 (1.64%)  1 3/61 (4.92%)  3
Tachycardia  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Sinus Tachycardia  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Ear and labyrinth disorders     
Ear Pain  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Tinnitus  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Vertigo  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Ear Deformity Acquired * 1  0/61 (0.00%)  0 1/61 (1.64%)  2
Tympanic Membrane Perforation  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Vertigo Positional  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Endocrine disorders     
Mineralocorticoid Deficiency  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Eye disorders     
Chalazion  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Vision Blurred  1  3/61 (4.92%)  3 1/61 (1.64%)  1
Foreign Body Sensation in Eyes  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Lacrimation Increased  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Gastrointestinal disorders     
Abdominal Pain  1  2/61 (3.28%)  2 2/61 (3.28%)  3
Abdominal Pain Upper  1  4/61 (6.56%)  7 0/61 (0.00%)  0
Constipation  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Dental Caries  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Epigastric Discomfort  1  1/61 (1.64%)  2 0/61 (0.00%)  0
Inguinal Hernia  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Nausea  1  8/61 (13.11%)  9 4/61 (6.56%)  5
Vomiting  1  4/61 (6.56%)  4 3/61 (4.92%)  4
Abdominal Pain Lower  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Diverticulum Intestinal  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Dyspepsia  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Faeces Soft  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Food Poisoning  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Gastrooesophageal Reflux Disease  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Diarrhoea  1  4/61 (6.56%)  6 3/61 (4.92%)  3
General disorders     
Asthenia  1  4/61 (6.56%)  6 3/61 (4.92%)  3
Chest Pain  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Fat Tissue Increased  1  1/61 (1.64%)  2 0/61 (0.00%)  0
Fatigue  1  9/61 (14.75%)  13 10/61 (16.39%)  20
Inflammation  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Influenza-like Illness  1  2/61 (3.28%)  3 4/61 (6.56%)  4
Malaise  1  5/61 (8.20%)  5 2/61 (3.28%)  2
Pyrexia  1  9/61 (14.75%)  9 4/61 (6.56%)  4
Therapeutic Response Unexpected  1 [1]  10/61 (16.39%)  15 1/61 (1.64%)  1
Thirst  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Oedema Peripheral  1  0/61 (0.00%)  0 1/61 (1.64%)  3
Peripheral Swelling  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Sensation of Foreign Body  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Infections and infestations     
Acute Sinusitis * 1  1/61 (1.64%)  1 0/61 (0.00%)  0
Bronchitis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Conjunctivitis viral  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Cystitis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Ear infection fungal  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Gastroenteritis  1  1/61 (1.64%)  1 4/61 (6.56%)  4
Gastroenteritis viral  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Influenza  1  2/61 (3.28%)  2 1/61 (1.64%)  1
Lower Respiratory Tract Infection  1  1/61 (1.64%)  2 0/61 (0.00%)  0
Nasopharyngitis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Otitis media  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Paronychia  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Pharyngitis  1  2/61 (3.28%)  2 0/61 (0.00%)  0
Sinusitis  1  2/61 (3.28%)  2 1/61 (1.64%)  1
Tonsilitis  1  2/61 (3.28%)  2 0/61 (0.00%)  0
Upper Respiratory Tract Infection  1  1/61 (1.64%)  1 3/61 (4.92%)  3
Urinary Tract Infection  1  4/61 (6.56%)  4 2/61 (3.28%)  2
Viral Infection  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Viral Upper Respiratory Tract Infection  1  12/61 (19.67%)  16 13/61 (21.31%)  15
Diarrhoea Infectious  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Oral Candidiasis  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Otitis Media Acute  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Tooth Infection  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Viral Rash  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Salpingitis  1  1/61 (1.64%)  2 0/61 (0.00%)  0
Herpes zoster  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Injury, poisoning and procedural complications     
Contusion  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Head Fracture  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Limb Injury  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Procedural Pain  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Auricular Haematoma  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Ear Injury  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Ligament Sprain  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Procedural Complication  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Sunburn  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Toxicity to Various Agents  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Wound  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Investigations     
Alanine Aminotransferase Increased  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Blood Sodium Decreased  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Body Temperature Increased  1  2/61 (3.28%)  2 0/61 (0.00%)  0
Osteocalcin Decreased  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Renin Increased  1  3/61 (4.92%)  3 7/61 (11.48%)  7
Urine Output Decreased  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Aspartate Aminotransferase Increased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Blood Creatine Phosphokinase Increased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Blood Glucose Increased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
C-Telopeptide Increased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Haematocrit Decreased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Haemoglobin Decreased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Liver Function Test Abnormal * 1  0/61 (0.00%)  0 1/61 (1.64%)  1
Weight Increased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
White Blood Cell Count Increased  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Metabolism and nutrition disorders     
Abnormal Loss of Weight  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Abnormal Weight Gain  1  3/61 (4.92%)  3 2/61 (3.28%)  2
Decreased Appetite  1  2/61 (3.28%)  2 0/61 (0.00%)  0
Fluid Retention  1  1/61 (1.64%)  1 2/61 (3.28%)  2
Gluten Sensitivity  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Hyperglycaemia  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Hyperinsulinaemia * 1  3/61 (4.92%)  3 1/61 (1.64%)  1
Impaired Fasting Glucose * 1  3/61 (4.92%)  3 1/61 (1.64%)  1
Increased Appetite * 1  5/61 (8.20%)  5 2/61 (3.28%)  2
Weight Fluctuation  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Alcohol Intolerance  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/61 (3.28%)  3 2/61 (3.28%)  2
Back Pain  1  4/61 (6.56%)  4 3/61 (4.92%)  3
Joint Stiffness  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Muscle Fatigue  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Muscle Spasms  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Muscle Tightness  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Muscular Weakness  1  2/61 (3.28%)  2 0/61 (0.00%)  0
Musculoskeletal Pain  1  2/61 (3.28%)  2 1/61 (1.64%)  1
Myalgia  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Neck Pain  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Osteoarthritis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Pain in Extremity  1  1/61 (1.64%)  2 1/61 (1.64%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal Cell Carcinoma  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Nervous system disorders     
Carpal Tunnel Syndrome  1  2/61 (3.28%)  2 0/61 (0.00%)  0
Circardian Rhythm Sleep Disorder  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Dizziness  1  7/61 (11.48%)  13 4/61 (6.56%)  5
Dizziness Postural  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Headache  1  15/61 (24.59%)  19 15/61 (24.59%)  22
Memory Impairment  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Migraine  1  1/61 (1.64%)  2 1/61 (1.64%)  1
Paraesthesia  1  2/61 (3.28%)  2 1/61 (1.64%)  1
Peripheral Nerve Lesion  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Poor Quality Sleep  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Sensory Loss  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Somnolence  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Lethargy  1  0/61 (0.00%)  0 1/61 (1.64%)  2
Psychomotor Hyperactivity  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Syncope  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Tension Headache  1  0/61 (0.00%)  0 2/61 (3.28%)  2
Tremor  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Psychiatric disorders     
Affect Lability  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Anxiety  1  1/61 (1.64%)  2 0/61 (0.00%)  0
Burnout Syndrome  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Depressed Mood  1  2/61 (3.28%)  2 1/61 (1.64%)  1
Depression  1  2/61 (3.28%)  3 2/61 (3.28%)  2
Insomnia  1  5/61 (8.20%)  6 4/61 (6.56%)  4
Irritability  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Libido Decreased  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Stress  1  1/61 (1.64%)  1 3/61 (4.92%)  3
Agitation  1  0/61 (0.00%)  0 2/61 (3.28%)  3
Emotional Distress  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Sleep Disorder  1  0/61 (0.00%)  0 2/61 (3.28%)  2
Reproductive system and breast disorders     
Menstruation Irregular  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Erectile Dysfunction  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Cough  1  3/61 (4.92%)  4 0/61 (0.00%)  0
Oropharyngeal Pain  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Rhinorrhoea  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Nasal Congestion  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Dyspnoea  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Skin and subcutaneous tissue disorders     
Acne  1  2/61 (3.28%)  2 0/61 (0.00%)  0
Alopecia  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Cold Sweat  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Eczema  1  1/61 (1.64%)  1 1/61 (1.64%)  1
Erythema  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Hair Growth Abnormal  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Hyperhidrosis  1  2/61 (3.28%)  2 1/61 (1.64%)  1
Psoriasis  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Rash  1  3/61 (4.92%)  3 0/61 (0.00%)  0
Urticaria  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Blister  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Chloasma * 1  0/61 (0.00%)  0 1/61 (1.64%)  1
Vascular disorders     
Haematoma  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Hypotension  1  1/61 (1.64%)  1 0/61 (0.00%)  0
Hypertension  1  0/61 (0.00%)  0 1/61 (1.64%)  1
Pallor  1  0/61 (0.00%)  0 1/61 (1.64%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
AE of unexpected therapeutic benefit
A limitation of the pre-defined primary endpoint was that it included an unsigned SDS score over a 24-hour period.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Specified in the contractual agreements between the Sponsor and investigators: "Neither the CRO, nor the Heath Board, nor the Investigator shall register the Clinical Trial, or the results, on any publicly accessible clinical trial registry."
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Information Line
Organization: Diurnal Limited
Phone: +44 (0) 2920 682069
EMail: info@diurnal.co.uk
Layout table for additonal information
Responsible Party: Diurnal Limited
ClinicalTrials.gov Identifier: NCT02716818     History of Changes
Other Study ID Numbers: DIUR-005
First Submitted: February 26, 2016
First Posted: March 23, 2016
Results First Submitted: July 10, 2019
Results First Posted: September 4, 2019
Last Update Posted: September 4, 2019