Congenital Adrenal Hyperplasia
Conditions
Keywords
Extension study
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.
Detailed description
All subjects will have a screening visit prior to the baseline assessment to allow DIUR-006 procedures to be fully explained and informed consent to be given by the subject. For subjects from DIUR-003 this screening visit will include safety blood tests. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be not be entered into the study. All subjects will then return for the baseline visit. For subjects entering from study DIUR-003 the full set of baseline assessments will be completed, including 2 blood samples (one at 09:00 and one at 13:00 hours) for 17-OHP and A4. For subjects entering from DIUR-005, test results from their last visit in the feeder study (Visit 4) will be used for this baseline assessment, with the 09:00 and 13:00 hour results taken from the 24-hour hormone profiles conducted at the visit. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be withdrawn from this study. Once the baseline assessments are completed, the subjects will be given sufficient Chronocort® to use until the next visit at Week 4. Subjects from study DIUR-005 who were previously on Chronocort® will continue on the same dose of Chronocort® that they were receiving at the end of the feeder study. Subjects from study DIUR-005 on standard therapy and subjects from study DIUR-003 will have their initial dose of Chronocort® determined using the hydrocortisone equivalent of baseline therapy. All subjects will return to the study centre at 4, 12 and 24 weeks after starting study DIUR-006 for additional blood tests and dose titration, if necessary. Visits thereafter will take place at 6-monthly intervals. If there is a change of dose, an interim visit or phone call will be needed inbetween the 6-monthly visits. All subjects will receive telephone calls at 3 monthly intervals, and unscheduled visits will be arranged if necessary. Subjects will also be provided with Chronocort® supplies from the study pharmacy at 3-monthly or 6-monthly intervals.
Interventions
DRUGHydrocortisone
Modified release hydrocortisone
Sponsors
Neurocrine UK Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects with CAH who have successfully completed a clinical trial with the current formulation of Chronocort®. 2. Provision of signed written informed consent.
Exclusion criteria
1. Co-morbid condition requiring daily administration of a medication (or use of any medications/supplements) that interferes with the metabolism of glucocorticoids. 2. 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\]). 3. Females who are pregnant or lactating. 4. Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH. 5. History of malignancy (other than basal cell carcinoma successfully treated \>6 months prior to entry into the study). 6. Subjects with a history of bilateral adrenalectomy. 7. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study, except for another clinical trial with the current formulation of Chronocort®. 8. Subjects unable to comply with the requirements of the protocol. 9. Subjects who routinely work night shifts and so do not sleep during the usual nighttime hours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability - Number of Participants With Adrenal Insufficiency | Up to approximately 5 years and 11 months | 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. |
| Safety and Tolerability - Number of Participants Who Used Sick Day Medication | Up to approximately 5 years and 11 months | 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. |
| Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis | Up to approximately 5 years and 11 months | 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). |
| Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Up to approximately 5 years and 11 months | 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. |
| Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Baseline up to approximately 5 years and 11 months | 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. |
| Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Baseline up to approximately 5 years and 11 months | 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. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Diastolic Blood Pressure | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Diastolic blood pressure. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Systolic Blood Pressure | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Systolic blood pressure. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Pulse Rate | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Pulse rate. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Respiratory Rate | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Respiratory rate. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - body temperature. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Body Weight. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - BMI | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - BMI. |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference | Baseline, Month 30 | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Waist circumference. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - total fat mass |
| Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18 | Baseline, Months 12 and 18 | The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Scores of the first four health items (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. Scores of last four items (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. |
| Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c) | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in HbA1c. |
| Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18 | Baseline, Months 12 and 18 | The EQ-5D questionnaire consists of 2 parts, the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression each with 5 problem levels (1-none to 5-extreme). The results from the dimensions were combined using a standard method specially designed for the EQ-5D questionnaire to give a single index value (EuroQol Research Foundation) with scores ranging from 0 (no problems) to 1 (extreme problems). The EQ VAS is a visual scale in which the participant gives a single score between 0 (worst health state) and 100 (best health state). |
| Number of Participants With Dose Titrations | Baseline to Week 4 and Month 18 | Long-term efficacy of Chronocort, as assessed by number of participants with dose titrations. Data are presented for number of participants with a dose increase, dose decrease, both a dose increase, and a dose decrease or no dose titration at specified timepoints. |
| Change From Pre-Chronocort Baseline in Quality of Life - Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI) Score at Months 12 and 18 | Baseline, Months 12 and 18 | MAF is a 16-item scale that measures fatigue according to 4 dimensions; degree and severity, distress that it causes, timing of fatigue, and its impact of various activities of daily living. The GFI score was calculated using a standard method specific to the MAF questionnaire. This combines the responses to the questionnaire to give one score ranging from 1 (no fatigue) to 50 (severe fatigue), with a higher score indicating more severe fatigue, fatigue distress, or impact on activities of daily living. Decreases from baseline indicate improvement. |
| 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 was summarized in mg/day of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. Baseline was defined as the first visit of Study DIUR-006 for all participants. |
| 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 | Total daily dose of Chronocort per BSA was summarized in mg/day/m\^2 of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. The BSA (m\^2) was calculated from baseline values using the Dubois formula \[weight (kg)\^0.425\] x \[Height (cm)\^0.725)\] x 0.007184. Baseline was defined as the first visit of Study DIUR-006 for all participants. |
| Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting glucose. |
| Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | Baseline and Week 24 | Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for 17-OHP. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the optimal range (defined as 1.2 to 36.4 nanomoles \[nmol\]/liter \[L\]) for 17-OHP. |
| Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | Baseline and Week 24 | Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for A4. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the reference range (defined as 1.4 to 5.2 nmol/L in males and 1.0 to 7.0 nmol/L in females) for A4. |
| Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers (osteocalcin). |
| Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - C-Terminal Cross-linked Telopeptide (CTX) | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers - CTX. |
| Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in total testosterone. |
| Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting insulin. |
| Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP) | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in hsCRP. |
| Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA) | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in PRA. |
| Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (Dual energy X-ray absorptiometry \[DEXA\]) - total lean mass |
| Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density | Baseline, Month 24 | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - bone mineral density. |
Countries
United States
Participant flow
Recruitment details
This was a Phase 3, open-label extension study. Participants who completed studies DIUR-003 (NCT01735617) or DIUR-005 (NCT02716818) were offered the opportunity to continue Chronocort® therapy in this study. After screening, all participants underwent a full set of baseline assessments before starting treatment in this extension study.
Participants by arm
| Arm | Count |
|---|---|
| Chronocort® Participants who entered immediately from Study DIUR-005 who were previously on Chronocort (modified release hydrocortisone) continued on the same dose of Chronocort that they had been receiving at the end of the feeder study. All other participants had their initial dose of Chronocort determined using the hydrocortisone equivalent of their current treatment (immediately prior to the baseline visit). Dosing was adjusted on an individual participant basis by investigators using symptoms and signs of disease with 17-OHP and androstenedione evaluation to guide dose adjustment. | 91 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Fertility Treatment | 2 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Pregnancy | 5 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Chronocort® |
|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 11.76 |
| Age, Customized >=18-<30 Years | 30 Participants |
| Age, Customized >=30-<50 Years | 44 Participants |
| Age, Customized >=50-<70 Years | 17 Participants |
| Age, Customized >=70 Years | 0 Participants |
| Body Mass Index (BMI) | 28.802 kg/square meter (m^2) STANDARD_DEVIATION 5.6692 |
| Body Surface Area (BSA) | 1.798 m^2 STANDARD_DEVIATION 0.2099 |
| Body Temperature | 36.44 degrees Celsius (°C) STANDARD_DEVIATION 0.427 |
| Body Weight | 75.58 kilograms (kg) STANDARD_DEVIATION 16.091 |
| Diastolic Blood Pressure | 70.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 10.79 |
| Height | 162 centimeters (cm) STANDARD_DEVIATION 9.87 |
| Number of Participants Hospitalized Within the Last 12 Months Prior to Enrolment No | 85 Participants |
| Number of Participants Hospitalized Within the Last 12 Months Prior to Enrolment Yes | 6 Participants |
| Number of Participants With Adrenal Crises in the Last Year None | 86 Participants |
| Number of Participants With Adrenal Crises in the Last Year One | 5 Participants |
| Pulse Rate | 71.1 beats/minute STANDARD_DEVIATION 12.16 |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 89 Participants |
| Respiratory Rate | 16.3 breaths/minute STANDARD_DEVIATION 2.85 |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 29 Participants |
| Systolic Blood Pressure | 120.4 mmHg STANDARD_DEVIATION 13.92 |
| Time Since Congenital Adrenal Hyperplasia (CAH) Diagnosis | 35.76 years STANDARD_DEVIATION 11.565 |
| Waist Circumference | 91.54 cm STANDARD_DEVIATION 14.81 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 91 |
| other Total, other adverse events | 90 / 91 |
| serious Total, serious adverse events | 28 / 91 |
Outcome results
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - BMI | 0.086 kg/m^2 | Standard Deviation 2.4248 |
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature | 0.03 °C | Standard Deviation 0.464 |
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight | 0.14 kg | Standard Deviation 6.115 |
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Diastolic Blood Pressure | 2.7 mmHg | Standard Deviation 11.34 |
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Pulse Rate | 0.2 beats/minute | Standard Deviation 12.38 |
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Respiratory Rate | -0.2 breaths/minute | Standard Deviation 3.41 |
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Systolic Blood Pressure | -0.1 mmHg | Standard Deviation 12.81 |
Primary
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.
Time frame: Baseline, Month 30
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference | 1.95 cm | Standard Deviation 7.1028 |
Primary
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).
Time frame: Up to approximately 5 years and 11 months
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chronocort® | Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis | 7 Participants |
Primary
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.
Time frame: Up to approximately 5 years and 11 months
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Number of Participants Who Used Sick Day Medication | Participants Taking Medication From Sick Day Packs | 79 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants Who Used Sick Day Medication | Participants Taking Medication That Was Not From Sick Day Packs | 47 Participants |
Primary
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.
Time frame: Up to approximately 5 years and 11 months
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Number of Participants With Adrenal Insufficiency | Due to GC over-replacement | 25 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adrenal Insufficiency | Due to GC under-replacement | 41 Participants |
Primary
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.
Time frame: Up to approximately 5 years and 11 months
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation | 6 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any SAE causally related to Chronocort | 2 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE | 90 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE causally related to Chronocort | 37 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to sick day rules | 80 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to sick day rules causally related to Chronocort | 1 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to adrenal crisis | 7 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to adrenal crisis causally related to Chronocort | 0 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE of unexpected therapeutic benefit | 21 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE of unexpected therapeutic benefit causally related to Chronocort | 20 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to death | 1 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to death causally related to Chronocort | 0 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation causally related to Chronocort | 3 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any serious adverse event (SAE) | 28 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation | 0 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any severe AE | 24 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any severe AE causally related to Chronocort | 0 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE associated with a dose increase | 6 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE associated with a dose increase causally related to Chronocort | 2 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE associated with a dose decrease | 7 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE associated with a dose decrease causally related to Chronocort | 5 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE associated with a dose interruption | 9 Participants |
| Chronocort® | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | Any AE associated with a dose interruption causally related to Chronocort | 0 Participants |
Primary
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.
Time frame: Baseline up to approximately 5 years and 11 months
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Number analyzed for each parameter = participants with a normal parameter value (within reference range) at baseline and also with at least one on-treatment value.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Mean cell haemoglobin concentration | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Blood urea nitrogen | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 84 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Red Blood Cell Count | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 6 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Red Blood Cell Count | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 71 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Haemoglobin | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 5 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Haemoglobin | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 66 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Haematocrit | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 5 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Haematocrit | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 70 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Red cell distribution width | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 17 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Red cell distribution width | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 53 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Mean corpuscular volume | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 3 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Mean corpuscular volume | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 82 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Mean cell haemoglobin | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 6 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Mean cell haemoglobin | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 76 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Mean cell haemoglobin concentration | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 81 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Platelet count | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 3 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Platelet count | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 78 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total White Blood Cell Count | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 10 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total White Blood Cell Count | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 72 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Lymphocyte count absolute | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Lymphocyte count absolute | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 78 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Lymphocyte count percentage (%) | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 9 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Lymphocyte count percentage (%) | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 55 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Monocyte count absolute | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Monocyte count absolute | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 78 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Monocyte count % | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Monocyte count % | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 79 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Neutrophil count absolute | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 8 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Neutrophil count absolute | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 70 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Neutrophil count % | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 15 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Neutrophil count % | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 57 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Basophil count absolute | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Basophil count absolute | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 83 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Basophil count % | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Basophil count % | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 82 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Eosinophil count absolute | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 7 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Eosinophil count absolute | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 69 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Eosinophil count % | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 12 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Eosinophil count % | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 69 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Sodium | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Sodium | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 86 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Potassium | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Potassium | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Chloride | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 7 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Chloride | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 69 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total carbon dioxide | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total carbon dioxide | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 79 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total calcium | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total calcium | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 83 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total magnesium | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 2 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total magnesium | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Inorganic phosphorus | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 5 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Inorganic phosphorus | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 65 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Creatinine | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 2 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Creatinine | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 75 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Blood urea nitrogen | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Fasting glucose | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 23 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Fasting glucose | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 49 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Uric acid | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 2 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Uric acid | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total protein | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total protein | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 60 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Albumin | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 2 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Albumin | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Alkaline phosphatase | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 2 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Alkaline phosphatase | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Alanine transaminase (ALT) / glutamate-pyruvate transaminase (GPT) | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 2 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Alanine transaminase (ALT) / glutamate-pyruvate transaminase (GPT) | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Aspartate aminotransferase (AST) / glutamic oxaloacetic transaminase (GOT) | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 3 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Aspartate aminotransferase (AST) / glutamic oxaloacetic transaminase (GOT) | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 84 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total creatine kinase | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 14 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total creatine kinase | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 71 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Lactate dehydrogenase | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Lactate dehydrogenase | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total bilirubin | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 7 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total bilirubin | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 80 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Direct bilirubin | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Direct bilirubin | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 86 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total cholesterol | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 36 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Total cholesterol | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 31 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | High Density Lipoprotein (HDL) cholesterol | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | High Density Lipoprotein (HDL) cholesterol | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Low density lipoprotein (LDL) cholesterol | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 24 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Low density lipoprotein (LDL) cholesterol | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 10 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Triglycerides | Shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 12 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | Triglycerides | No shift from pre-Chronocort baseline within reference range to above reference range on-treatment | 72 Participants |
Primary
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.
Time frame: Baseline up to approximately 5 years and 11 months
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Number analyzed for each parameter = participants with a normal parameter value (within reference range) at baseline and also with at least one on-treatment value.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Sodium | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 6 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Sodium | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 81 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Potassium | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Potassium | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 81 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Chloride | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Chloride | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 75 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total carbon dioxide | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 3 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total carbon dioxide | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 77 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total calcium | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total calcium | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 80 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total magnesium | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total magnesium | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Inorganic phosphorus | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 7 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Blood urea nitrogen | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 3 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total protein | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total protein | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 57 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Albumin | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Albumin | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Alkaline phosphatase | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 2 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Alkaline phosphatase | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Alanine transaminase (ALT) / glutamate-pyruvate transaminase (GPT) | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Alanine transaminase (ALT) / glutamate-pyruvate transaminase (GPT) | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Aspartate aminotransferase (AST) / glutamic oxaloacetic transaminase (GOT) | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Aspartate aminotransferase (AST) / glutamic oxaloacetic transaminase (GOT) | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total creatine kinase | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total creatine kinase | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 85 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Lactate dehydrogenase | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Lactate dehydrogenase | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total bilirubin | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total bilirubin | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Direct bilirubin | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Direct bilirubin | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 87 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total cholesterol | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 3 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total cholesterol | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 64 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | High Density Lipoprotein (HDL) cholesterol | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | High Density Lipoprotein (HDL) cholesterol | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 81 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Low density lipoprotein (LDL) cholesterol | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Triglycerides | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 84 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Red Blood Cell Count | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 5 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Red Blood Cell Count | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 72 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Haemoglobin | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 13 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Haemoglobin | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 58 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Haematocrit | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 12 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Haematocrit | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 63 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Red cell distribution width | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Red cell distribution width | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 69 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Mean corpuscular volume | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 3 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Mean corpuscular volume | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 82 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Mean cell haemoglobin | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 5 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Mean cell haemoglobin | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 77 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Mean cell haemoglobin concentration | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 13 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Mean cell haemoglobin concentration | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 69 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Platelet count | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 1 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Platelet count | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 80 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total White Blood Cell Count | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 8 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Total White Blood Cell Count | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 74 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Lymphocyte count absolute | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Lymphocyte count absolute | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 79 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Lymphocyte count % | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 12 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Lymphocyte count % | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 52 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Monocyte count absolute | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 10 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Monocyte count absolute | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 68 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Monocyte count % | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Monocyte count % | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 83 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Neutrophil count absolute | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 10 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Neutrophil count absolute | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 68 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Neutrophil count % | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 10 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Neutrophil count % | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 62 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Basophil count absolute | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Basophil count absolute | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 83 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Basophil count % | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Basophil count % | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 82 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Eosinophil count absolute | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 13 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Eosinophil count absolute | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 63 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Eosinophil count % | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Eosinophil count % | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 81 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Inorganic phosphorus | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 63 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Creatinine | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 12 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Creatinine | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 65 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Blood urea nitrogen | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 82 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Fasting glucose | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Fasting glucose | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 68 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Uric acid | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 4 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Uric acid | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 83 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Low density lipoprotein (LDL) cholesterol | No shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 30 Participants |
| Chronocort® | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | Triglycerides | Shift from pre-Chronocort baseline within reference range to below reference range on-treatment | 0 Participants |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - bone mineral density.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density | Bone Mineral Density, Baseline | 1.0940 grams (g)/square centimeter (cm^2) | Standard Deviation 0.09288 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density | Bone Mineral Density, Change at Month 24 | -0.0008 grams (g)/square centimeter (cm^2) | Standard Deviation 0.0362 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - total fat mass
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass | Total fat mass, Baseline | 27.943 kg | Standard Deviation 11.5289 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass | Total fat mass, Change at Month 24 | 0.811 kg | Standard Deviation 5.332 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (Dual energy X-ray absorptiometry \[DEXA\]) - total lean mass
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass | Total lean mass, Baseline | 45.819 kg | Standard Deviation 9.3395 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass | Total lean mass, Change at Month 24 | -0.563 kg | Standard Deviation 2.949 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - C-Terminal Cross-linked Telopeptide (CTX)
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers - CTX.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - C-Terminal Cross-linked Telopeptide (CTX) | CTX, Baseline | 540.1 nanograms (ng)/L | Standard Deviation 251.84 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - C-Terminal Cross-linked Telopeptide (CTX) | CTX, Change at Month 24 | -43.6 nanograms (ng)/L | Standard Deviation 228.53 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers (osteocalcin).
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin | Osteocalcin, Baseline | 19.486 micrograms (µg)/L | Standard Deviation 7.8596 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin | Osteocalcin, Change at Month 24 | 3.535 micrograms (µg)/L | Standard Deviation 10.4837 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting glucose.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose | Fasting glucose, Baseline | 5.09 millimoles (mmol)/L | Standard Deviation 0.434 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose | Fasting glucose, Change at Month 24 | -0.02 millimoles (mmol)/L | Standard Deviation 0.534 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting insulin.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin | Fasting insulin, Baseline | 77.8 picomoles (pmol)/L | Standard Deviation 35.61 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin | Fasting insulin, Change at Month 24 | -6.1 picomoles (pmol)/L | Standard Deviation 36.41 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c)
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in HbA1c.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c) | HbA1c, Baseline | 5.17 percentage of HbA1c | Standard Deviation 0.312 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c) | HbA1c, Change at Month 24 | 0.12 percentage of HbA1c | Standard Deviation 0.235 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP)
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in hsCRP.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP) | hsCRP, Baseline | 1.78 mg/L | Standard Deviation 5.01 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP) | hsCRP, Change at Month 24 | 0.56 mg/L | Standard Deviation 6.29 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA)
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in PRA.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA) | PRA, Baseline | 0.878 ng/liter (L)/second | Standard Deviation 0.9587 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA) | PRA, Change at Month 24 | 0.010 ng/liter (L)/second | Standard Deviation 1.2575 |
Secondary
Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone
Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in total testosterone.
Time frame: Baseline, Month 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. Overall number of participants analyzed = number of male or female participants with evaluable data for the outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone | Total Testosterone, Baseline | 17.1490 nmol/L | Standard Deviation 8.64256 |
| Chronocort® | Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone | Total Testosterone, Change at Month 24 | -1.5850 nmol/L | Standard Deviation 6.51899 |
| Chronocort® - Females | Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone | Total Testosterone, Change at Month 24 | -0.2892 nmol/L | Standard Deviation 1.1189 |
| Chronocort® - Females | Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone | Total Testosterone, Baseline | 0.9535 nmol/L | Standard Deviation 1.3875 |
Secondary
Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18
The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Scores of the first four health items (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. Scores of last four items (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
Time frame: Baseline, Months 12 and 18
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18 | MCS, Change at Month 18 | 0.257 units on a scale | Standard Deviation 11.7003 |
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18 | PCS, Change at Month 12 | 0.496 units on a scale | Standard Deviation 5.7091 |
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18 | PCS, Change at Month 18 | 0.516 units on a scale | Standard Deviation 6.8678 |
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18 | MCS, Change at Month 12 | 0.362 units on a scale | Standard Deviation 12.3736 |
Secondary
Change From Pre-Chronocort Baseline in Quality of Life - Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI) Score at Months 12 and 18
MAF is a 16-item scale that measures fatigue according to 4 dimensions; degree and severity, distress that it causes, timing of fatigue, and its impact of various activities of daily living. The GFI score was calculated using a standard method specific to the MAF questionnaire. This combines the responses to the questionnaire to give one score ranging from 1 (no fatigue) to 50 (severe fatigue), with a higher score indicating more severe fatigue, fatigue distress, or impact on activities of daily living. Decreases from baseline indicate improvement.
Time frame: Baseline, Months 12 and 18
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI) Score at Months 12 and 18 | GFI, Change at Month 12 | -1.76 units on a scale | Standard Deviation 11.939 |
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI) Score at Months 12 and 18 | GFI, Change at Month 18 | -2.21 units on a scale | Standard Deviation 12.847 |
Secondary
Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18
The EQ-5D questionnaire consists of 2 parts, the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression each with 5 problem levels (1-none to 5-extreme). The results from the dimensions were combined using a standard method specially designed for the EQ-5D questionnaire to give a single index value (EuroQol Research Foundation) with scores ranging from 0 (no problems) to 1 (extreme problems). The EQ VAS is a visual scale in which the participant gives a single score between 0 (worst health state) and 100 (best health state).
Time frame: Baseline, Months 12 and 18
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18 | EQ-5D-5L Index Score, Change at Month 18 | -0.004 units on a scale | Standard Deviation 0.1641 |
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18 | EQ VAS Score, Change at Month 12 | 1.529 units on a scale | Standard Deviation 16.8612 |
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18 | EQ VAS Score, Change at Month 18 | 1.819 units on a scale | Standard Deviation 15.7218 |
| Chronocort® | Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18 | EQ-5D-5L Index Score, Change at Month 12 | -0.022 units on a scale | Standard Deviation 0.1766 |
Secondary
Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP)
Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for 17-OHP. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the optimal range (defined as 1.2 to 36.4 nanomoles \[nmol\]/liter \[L\]) for 17-OHP.
Time frame: Baseline and Week 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 09:00 17-OHP : Baseline | Non-responder | 39 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 09:00 17-OHP : Week 24 | Responder | 54 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 09:00 17-OHP : Week 24 | Non-responder | 33 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 13:00 17-OHP : Baseline | Responder | 64 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 13:00 17-OHP : Baseline | Non-responder | 27 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 13:00 17-OHP : Week 24 | Responder | 64 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 13:00 17-OHP : Week 24 | Non-responder | 23 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | 09:00 17-OHP : Baseline | Responder | 51 Participants |
Secondary
Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4)
Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for A4. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the reference range (defined as 1.4 to 5.2 nmol/L in males and 1.0 to 7.0 nmol/L in females) for A4.
Time frame: Baseline and Week 24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 09:00 A4 : Baseline | Responder | 48 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 09:00 A4 : Baseline | Non-responder | 42 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 09:00 A4 : Week 24 | Responder | 49 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 09:00 A4 : Week 24 | Non-responder | 38 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 13:00 A4 : Baseline | Responder | 43 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 13:00 A4 : Baseline | Non-responder | 48 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 13:00 A4 : Week 24 | Responder | 39 Participants |
| Chronocort® | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | 13:00 A4 : Week 24 | Non-responder | 48 Participants |
Secondary
Number of Participants With Dose Titrations
Long-term efficacy of Chronocort, as assessed by number of participants with dose titrations. Data are presented for number of participants with a dose increase, dose decrease, both a dose increase, and a dose decrease or no dose titration at specified timepoints.
Time frame: Baseline to Week 4 and Month 18
Population: Full Analysis Set. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Chronocort® | Number of Participants With Dose Titrations | Month 18 | Had both a dose increase and a dose decrease | 0 Participants |
| Chronocort® | Number of Participants With Dose Titrations | Month 18 | No dose titration | 64 Participants |
| Chronocort® | Number of Participants With Dose Titrations | Baseline to Week 4 | Dose increase | 0 Participants |
| Chronocort® | Number of Participants With Dose Titrations | Baseline to Week 4 | Dose decrease | 0 Participants |
| Chronocort® | Number of Participants With Dose Titrations | Baseline to Week 4 | Had both a dose increase and a dose decrease | 0 Participants |
| Chronocort® | Number of Participants With Dose Titrations | Baseline to Week 4 | No dose titration | 91 Participants |
| Chronocort® | Number of Participants With Dose Titrations | Month 18 | Dose increase | 2 Participants |
| Chronocort® | Number of Participants With Dose Titrations | Month 18 | Dose decrease | 17 Participants |
Secondary
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
Total daily dose of Chronocort per BSA was summarized in mg/day/m\^2 of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. The BSA (m\^2) was calculated from baseline values using the Dubois formula \[weight (kg)\^0.425\] x \[Height (cm)\^0.725)\] x 0.007184. Baseline was defined as the first visit of Study DIUR-006 for all participants.
Time frame: Baseline to Week 4 and Month 18-24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Chronocort® | 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 | 15.764 mg/day/m^2 |
| Chronocort® | 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 | Month 18 - Month 24 | 11.766 mg/day/m^2 |
Secondary
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
Total daily dose was summarized in mg/day of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. Baseline was defined as the first visit of Study DIUR-006 for all participants.
Time frame: Baseline to Week 4 and Month 18-24
Population: The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Chronocort® | 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 | 30.00 mg/day |
| Chronocort® | 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 | Month 18 - Month 24 | 20.00 mg/day |