Trial Outcomes & Findings for A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH (NCT NCT03062280)

Last Updated: 2024-10-28

Results Overview

Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - body temperature.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

91 participants

Primary outcome timeframe

Baseline, Month 30

Results posted on

2024-10-28

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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-hydroxyprogesterone (17-OHP) and androstenedione evaluation to guide dose adjustment.
Overall Study STARTED	91
Overall Study COMPLETED	69
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	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-hydroxyprogesterone (17-OHP) and androstenedione evaluation to guide dose adjustment.
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

A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chronocort® n=91 Participants 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.
Age, Continuous	37.1 years STANDARD_DEVIATION 11.76 • n=5 Participants
Age, Customized >=18-<30 Years	30 Participants n=5 Participants
Age, Customized >=30-<50 Years	44 Participants n=5 Participants
Age, Customized >=50-<70 Years	17 Participants n=5 Participants
Age, Customized >=70 Years	0 Participants n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Race/Ethnicity, Customized White	89 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska native	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Height	162 centimeters (cm) STANDARD_DEVIATION 9.87 • n=5 Participants
Body Weight	75.58 kilograms (kg) STANDARD_DEVIATION 16.091 • n=5 Participants
Body Mass Index (BMI)	28.802 kg/square meter (m^2) STANDARD_DEVIATION 5.6692 • n=5 Participants
Body Surface Area (BSA)	1.798 m^2 STANDARD_DEVIATION 0.2099 • n=5 Participants
Waist Circumference	91.54 cm STANDARD_DEVIATION 14.810 • n=5 Participants
Time Since Congenital Adrenal Hyperplasia (CAH) Diagnosis	35.76 years STANDARD_DEVIATION 11.565 • n=5 Participants
Number of Participants Hospitalized Within the Last 12 Months Prior to Enrolment Yes	6 Participants n=5 Participants
Number of Participants Hospitalized Within the Last 12 Months Prior to Enrolment No	85 Participants n=5 Participants
Number of Participants With Adrenal Crises in the Last Year None	86 Participants n=5 Participants
Number of Participants With Adrenal Crises in the Last Year One	5 Participants n=5 Participants
Diastolic Blood Pressure	70.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 10.79 • n=5 Participants
Systolic Blood Pressure	120.4 mmHg STANDARD_DEVIATION 13.92 • n=5 Participants
Pulse Rate	71.1 beats/minute STANDARD_DEVIATION 12.16 • n=5 Participants
Respiratory Rate	16.3 breaths/minute STANDARD_DEVIATION 2.85 • n=5 Participants
Body Temperature	36.44 degrees Celsius (°C) STANDARD_DEVIATION 0.427 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Safety and Tolerability - Number of Participants With Adrenal Insufficiency Due to GC under-replacement	41 Participants	—
Safety and Tolerability - Number of Participants With Adrenal Insufficiency Due to GC over-replacement	25 Participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Safety and Tolerability - Number of Participants Who Used Sick Day Medication Participants Taking Medication From Sick Day Packs	79 Participants	—
Safety and Tolerability - Number of Participants Who Used Sick Day Medication Participants Taking Medication That Was Not From Sick Day Packs	47 Participants	—

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis	7 Participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE	90 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE causally related to Chronocort	37 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to sick day rules causally related to Chronocort	1 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to adrenal crisis causally related to Chronocort	0 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE of unexpected therapeutic benefit causally related to Chronocort	20 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to death	1 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE associated with a dose increase causally related to Chronocort	2 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE associated with a dose decrease	7 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE associated with a dose interruption causally related to Chronocort	0 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to sick day rules	80 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to adrenal crisis	7 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE of unexpected therapeutic benefit	21 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to death causally related to Chronocort	0 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation	6 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation causally related to Chronocort	3 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any serious adverse event (SAE)	28 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any SAE causally related to Chronocort	2 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any SAE leading to discontinuation	0 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any severe AE	24 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any severe AE causally related to Chronocort	0 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE associated with a dose increase	6 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE associated with a dose decrease causally related to Chronocort	5 Participants	—
Safety and Tolerability - Number of Participants With Adverse Events (AEs) Any AE associated with a dose interruption	9 Participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=87 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=87 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature	0.03 °C Standard Deviation 0.464	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight	0.14 kg Standard Deviation 6.115	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=70 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference	1.95 cm Standard Deviation 7.1028	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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 Interval 10.0 to 55.0	—
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 Interval 6.8 to 55.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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 Interval 4.3 to 26.74	—
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 Interval 6.28 to 30.6	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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	—
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	—
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	—
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	—
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	—
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	—
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	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) 09:00 A4 : Baseline · Responder	48 Participants	—
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	—
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	—
Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) 13:00 A4 : Baseline · Responder	43 Participants	—
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	—
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	—
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 outcome

Timeframe: Baseline, Month 24

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers (osteocalcin).

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin Osteocalcin, Baseline	19.486 micrograms (µg)/L Standard Deviation 7.8596	—

SECONDARY outcome

Timeframe: Baseline, Month 24

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers - CTX.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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 outcome

Timeframe: 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.

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in total testosterone.

Outcome measures

Outcome measures
Measure	Chronocort® n=29 Participants 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.	Chronocort® - Females n=62 Participants Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone Total Testosterone, Baseline	17.1490 nmol/L Standard Deviation 8.64256	0.9535 nmol/L Standard Deviation 1.38750
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	-0.2892 nmol/L Standard Deviation 1.11890

SECONDARY outcome

Timeframe: 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.

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting insulin.

Outcome measures

Outcome measures
Measure	Chronocort® n=90 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin Fasting insulin, Baseline	77.8 picomoles (pmol)/L Standard Deviation 35.61	—
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 outcome

Timeframe: 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.

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting glucose.

Outcome measures

Outcome measures
Measure	Chronocort® n=90 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose Fasting glucose, Baseline	5.09 millimoles (mmol)/L Standard Deviation 0.434	—
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 outcome

Timeframe: Baseline, Month 24

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in HbA1c.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c) HbA1c, Baseline	5.17 percentage of HbA1c Standard Deviation 0.312	—
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 outcome

Timeframe: Baseline, Month 24

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in hsCRP.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP) hsCRP, Baseline	1.78 mg/L Standard Deviation 5.010	—
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 6.290	—

SECONDARY outcome

Timeframe: 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.

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in PRA.

Outcome measures

Outcome measures
Measure	Chronocort® n=90 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Chronocort® n=71 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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 2.9490	—

SECONDARY outcome

Timeframe: 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.

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - bone mineral density.

Outcome measures

Outcome measures
Measure	Chronocort® n=65 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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 0.03620	—

SECONDARY outcome

Timeframe: 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.

Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - total fat mass

Outcome measures

Outcome measures
Measure	Chronocort® n=71 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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 5.3320	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=84 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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	—
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	—
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	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=85 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Chronocort® n=85 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
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	—
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	—
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	—
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	—

SECONDARY outcome

Timeframe: Baseline to Week 4 and Month 18

Population: Full Analysis Set. 'Number analyzed' signifies participants evaluable at specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Chronocort® n=91 Participants 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.	Chronocort® - Females Females Chronocort® modified release hydrocortisone Hydrocortisone: Modified release hydrocortisone
Number of Participants With Dose Titrations Month 18 · No dose titration	64 Participants	—
Number of Participants With Dose Titrations Baseline to Week 4 · Dose increase	0 Participants	—
Number of Participants With Dose Titrations Baseline to Week 4 · Dose decrease	0 Participants	—
Number of Participants With Dose Titrations Baseline to Week 4 · Had both a dose increase and a dose decrease	0 Participants	—
Number of Participants With Dose Titrations Baseline to Week 4 · No dose titration	91 Participants	—
Number of Participants With Dose Titrations Month 18 · Dose increase	2 Participants	—
Number of Participants With Dose Titrations Month 18 · Dose decrease	17 Participants	—
Number of Participants With Dose Titrations Month 18 · Had both a dose increase and a dose decrease	0 Participants	—

Adverse Events

Chronocort®

Serious events: 28 serious events

Other events: 90 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Chronocort® n=91 participants at risk 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.
Infections and infestations Appendicitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations COVID-19	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Gastroenteritis	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Gastroenteritis norovirus	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Gastroenteritis viral	2.2% 2/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Influenza	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Kidney infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Lower respiratory tract infection	2.2% 2/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Pharyngitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Pneumonia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Urinary tract infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangiopericytoma	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant haemangiopericytoma metastatic	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Endocrine disorders Adrenal insufficiency	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Endocrine disorders Adrenocortical insufficiency acute	3.3% 3/91 • Number of events 9 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Anxiety	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Suicide attempt	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Depressed level of consciousness	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Dizziness	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Loss of consciousness	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Syncope	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Cardiac disorders Myocardial infarction	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Vascular disorders Brachiocephalic vein thrombosis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Vascular disorders Haematoma	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Asthma	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Abdominal discomfort	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Abdominal pain	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Diarrhoea	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Diverticulum	3.3% 3/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Melaena	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Vomiting	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	2.2% 2/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Pregnancy, puerperium and perinatal conditions Neonatal disorder	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Vulvovaginal inflammation	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Asthenia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Fatigue	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Pyrexia	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood potassium decreased	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Red blood cell microcytes	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Contusion	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Fall	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Hip fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Joint dislocation	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Subcutaneous haematoma	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Surgical and medical procedures Knee arthroplasty	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.

Other adverse events

Other adverse events
Measure	Chronocort® n=91 participants at risk 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.
Infections and infestations Acute sinusitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Appendicitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Bacterial vaginosis	3.2% 2/62 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Balanitis candida	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Bronchitis	11.0% 10/91 • Number of events 23 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations COVID-19	18.7% 17/91 • Number of events 18 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Candida infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Cystitis	4.4% 4/91 • Number of events 8 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Device related infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Ear infection	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Fungal infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Fungal skin infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Gastroenteritis	25.3% 23/91 • Number of events 27 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Gastroenteritis norovirus	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Gastroenteritis viral	6.6% 6/91 • Number of events 6 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Gingivitis	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Helicobacter infection	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Herpes zoster	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Influenza	33.0% 30/91 • Number of events 54 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Localised infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Lower respiratory tract infection	8.8% 8/91 • Number of events 12 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Nasopharyngitis	37.4% 34/91 • Number of events 105 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Oral candidiasis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Oral herpes	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Otitis externa	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Otitis media	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Pharyngitis	7.7% 7/91 • Number of events 7 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Pharyngitis streptococcal	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Pneumonia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Pulpitis dental	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Rhinitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Sinusitis	9.9% 9/91 • Number of events 16 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Staphylococcal infection	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Tonsillitis	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Tooth abscess	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Tooth infection	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Upper respiratory tract infection	12.1% 11/91 • Number of events 16 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Urinary tract infection	13.2% 12/91 • Number of events 13 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Viral infection	3.3% 3/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Vulval abscess	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Vulvovaginal candidiasis	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Vulvovaginal mycotic infection	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Infections and infestations Vulvovaginitis	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal rest tumour of the testis	3.4% 1/29 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the small bowel	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Blood and lymphatic system disorders Anaemia	4.4% 4/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Blood and lymphatic system disorders Iron deficiency anaemia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Blood and lymphatic system disorders Lymphadenopathy	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Immune system disorders Allergy to arthropod bite	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Immune system disorders Allergy to chemicals	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Immune system disorders Seasonal allergy	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Endocrine disorders Thyroid mass	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Endocrine disorders Thyroiditis subacute	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Abnormal weight gain	7.7% 7/91 • Number of events 7 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Decreased appetite	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Dehydration	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Hypercholesterolaemia	4.4% 4/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Increased appetite	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Iron deficiency	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Type 2 diabetes mellitus	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Vitamin B12 deficiency	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Vitamin D deficiency	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Adjustment disorder	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Anticipatory anxiety	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Anxiety	7.7% 7/91 • Number of events 11 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Bipolar I disorder	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Depressed mood	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Depression	11.0% 10/91 • Number of events 11 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Insomnia	22.0% 20/91 • Number of events 23 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Libido decreased	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Panic attack	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Sleep disorder	2.2% 2/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Psychiatric disorders Stress	9.9% 9/91 • Number of events 16 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Ageusia	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Anosmia	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Carpal tunnel syndrome	11.0% 10/91 • Number of events 12 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Circadian rhythm sleep disorder	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Clumsiness	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Disturbance in attention	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Dizziness	16.5% 15/91 • Number of events 25 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Headache	40.7% 37/91 • Number of events 66 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Hypoaesthesia	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Lethargy	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Memory impairment	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Migraine	5.5% 5/91 • Number of events 21 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Paraesthesia	9.9% 9/91 • Number of events 9 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Paresthesia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Poor quality sleep	2.2% 2/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Presyncope	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Seizure	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Somnolence	2.2% 2/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Syncope	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Taste disorder	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Tension headache	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Tremor	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Cataract	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Dry eye	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Episcleritis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Ocular hyperaemia	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Optic ischaemic neuropathy	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Vision blurred	4.4% 4/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Vitreous floaters	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Ear and labyrinth disorders Ear pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Ear and labyrinth disorders Excessive cerumen production	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Ear and labyrinth disorders Tinnitus	1.1% 1/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Ear and labyrinth disorders Tympanic membrane perforation	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Ear and labyrinth disorders Vertigo	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Cardiac disorders Palpitations	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Cardiac disorders Rebound tachycardia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Vascular disorders Haematoma	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Vascular disorders Hypertension	5.5% 5/91 • Number of events 6 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Vascular disorders Peripheral venous disease	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Cough	9.9% 9/91 • Number of events 12 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.6% 6/91 • Number of events 6 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.3% 3/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.9% 9/91 • Number of events 13 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Respiration abnormal	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Respiratory, thoracic and mediastinal disorders productive cough	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Abdominal distension	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Abdominal pain	5.5% 5/91 • Number of events 8 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Abdominal pain upper	11.0% 10/91 • Number of events 15 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Anal pruritus	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Colitis ulcerative	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Constipation	4.4% 4/91 • Number of events 6 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Diarrhoea	29.7% 27/91 • Number of events 63 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Diverticulum	3.3% 3/91 • Number of events 7 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Dyspepsia	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Dysphagia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Flatulence	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Food poisoning	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Gastritis	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Haemorrhoidal haemorrhage	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Hiatus hernia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Mouth ulceration	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Nausea	22.0% 20/91 • Number of events 26 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Oesophagitis	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Oral disorder	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Oral pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Proctalgia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Teeth brittle	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Toothache	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Vomiting	34.1% 31/91 • Number of events 48 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Acne	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Alopecia areata	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Cold sweat	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Dermatosis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Dry skin	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Eczema	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.5% 5/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Hyperkeratosis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Lichen planus	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Lichen sclerosus	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Night sweats	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Pruritus	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Psoriasis	2.2% 2/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Rash	8.8% 8/91 • Number of events 9 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Skin laxity	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Skin lesion	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Skin striae	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Urticaria	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Arthralgia	15.4% 14/91 • Number of events 16 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Axillary mass	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Back pain	17.6% 16/91 • Number of events 22 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Bursitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Flank pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Joint effusion	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Joint stiffness	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Joint swelling	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Limb mass	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Muscle spasms	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Muscular weakness	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Myalgia	6.6% 6/91 • Number of events 6 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Myositis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Neck pain	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Osteoarthritis	4.4% 4/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Osteoporosis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 13/91 • Number of events 15 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Plantar fasciitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Synovial cyst	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Tendonitis	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Trigger finger	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Renal and urinary disorders Nephrolithiasis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Renal and urinary disorders Polyuria	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Renal and urinary disorders Renal pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Amenorrhoea	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Azoospermia	3.4% 1/29 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Breast pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Breast tenderness	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Dysmenorrhoea	4.8% 3/62 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Endometrial hyperplasia	4.8% 3/62 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Gynaecomastia	3.4% 1/29 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Menometrorrhagia	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Menopausal symptoms	3.2% 2/62 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Menorrhagia	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Menstruation irregular	12.9% 8/62 • Number of events 10 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Metrorrhagia	4.8% 3/62 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Ovarian cyst	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Pelvic pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Premature menopause	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Testicular mass	6.9% 2/29 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Testicular pain	3.4% 1/29 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Vaginal haemorrhage	3.2% 2/62 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Vulvar melanosis	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Vulvovaginal pruritus	1.6% 1/62 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Congenital, familial and genetic disorders BRCA1 gene mutation	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Asthenia	15.4% 14/91 • Number of events 21 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Chills	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Facial pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Fatigue	47.3% 43/91 • Number of events 106 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Feeling abnormal	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Gait disturbance	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Injection site dermatitis	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Malaise	12.1% 11/91 • Number of events 16 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Oedema mucosal	1.1% 1/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Oedema peripheral	5.5% 5/91 • Number of events 8 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Pain	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Performance status decreased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Peripheral swelling	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Pyrexia	40.7% 37/91 • Number of events 66 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Swelling	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Swelling face	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Therapeutic response unexpected	29.7% 27/91 • Number of events 46 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Vaccination site pain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
General disorders Vaccination site swelling	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood androstenedione increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood cholesterol increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood creatine phosphokinase increased	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood glucose increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood potassium decreased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood potassium increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood sodium decreased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood testosterone decreased	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Blood testosterone increased	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Bone density decreased	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Bone density increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations C-reactive protein increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Eosinophil count decreased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Haematocrit decreased	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Haemoglobin decreased	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Heart rate decreased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Liver function test abnormal	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Low density lipoprotein increased	4.4% 4/91 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Occult blood	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Red blood cell count decreased	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Red blood cell microcytes	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Renin decreased	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Renin increased	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations Weight increased	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations White blood cell count increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Arthropod bite	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Bone contusion	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Contusion	1.1% 1/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Corneal abrasion	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Eye injury	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Fall	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Fibula fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Foot fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Hand fracture	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Heat stroke	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Hypobarism	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Joint dislocation	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Ligament rupture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Ligament sprain	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Limb injury	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Maternal exposure during pregnancy	8.1% 5/62 • Number of events 6 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Meniscus injury	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Mouth injury	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Muscle strain	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Patella fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Paternal exposure before pregnancy	10.3% 3/29 • Number of events 5 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Post-traumatic neck syndrome	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Procedural nausea	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Procedural pain	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Procedural vomiting	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Radius fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Rib fracture	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Skin abrasion	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Skin laceration	4.4% 4/91 • Number of events 4 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Spinal fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Thermal burn	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Tooth fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Upper limb fracture	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Injury, poisoning and procedural complications Vaccination complication	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Surgical and medical procedures COVID-19 immunisation	18.7% 17/91 • Number of events 24 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Surgical and medical procedures Gingival graft	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Surgical and medical procedures Tooth extraction	3.3% 3/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Social circumstances Educational problem	2.2% 2/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Surgical and medical procedures Family stress	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Social circumstances Impaired work ability	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Social circumstances Physical assault	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Social circumstances Stress at work	2.2% 2/91 • Number of events 3 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Ear and labyrinth disorders Ear deformity acquired	1.1% 1/91 • Number of events 2 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Foreign body sensation in eyes	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Eye disorders Lacrimation increased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Gastrointestinal disorders Inguinal hernia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Investigations c-reactive protein decreased	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Alcohol intolerance	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Gluten sensitivity	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Hyperinsulinaemia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Metabolism and nutrition disorders Impaired fasting glucose	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Musculoskeletal and connective tissue disorders Osteopenia	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Nervous system disorders Sensory loss	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Reproductive system and breast disorders Erectile dysfunction	3.4% 1/29 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
Skin and subcutaneous tissue disorders Blister	1.1% 1/91 • Number of events 1 • From first dose of study drug administration up to approximately 5 years and 11 months The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.

Additional Information

Clinical Trials Information

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Principal investigator is a sponsor employee Sponsor \& PI will prepare of manuscripts. Comments on publications will be considered by authors. Publications will not include company confidential details without Sponsor permission. Summary data may be announced to comply with Financial \& Regulatory Authorities, while ensuring this will not impact the investigator's ability to publish. Announcements made prior to publication will be reviewed \& approved by PI. Data from individual sites will only be published under exceptional circumstances.
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