Trial Outcomes & Findings for XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors (NCT NCT00088166)

Last Updated: 2014-08-13

Results Overview

The primary efficacy endpoint was the proportion of patients in each treatment group who were Responders at Week 2 and who continued to be Responders at Week 5. Responders were defined as study patients who demonstrated the following: * 50% or greater reduction in dexamethasone dose relative to Baseline * Overall 10-Item Neurological Examination Score unchanged or lower compared to Baseline * Karnofsky Score unchanged or increased relative to Baseline

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

200 participants

Primary outcome timeframe

Prospective

Results posted on

2014-08-13

Participant Flow

Participant milestones

Participant milestones
Measure	hCRF Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Overall Study STARTED	100	100
Overall Study COMPLETED	47	39
Overall Study NOT COMPLETED	53	61

Reasons for withdrawal

Reasons for withdrawal
Measure	hCRF Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Overall Study Adverse Event	11	9
Overall Study Death	3	1
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	4	1
Overall Study Protocol Violation	1	5
Overall Study Patient deterioration	29	39
Overall Study Withdrawal by Subject	5	5

Baseline Characteristics

XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	hCRF n=100 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=100 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking	Total n=200 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	89 Participants n=99 Participants	87 Participants n=107 Participants	176 Participants n=206 Participants
Age, Categorical >=65 years	11 Participants n=99 Participants	13 Participants n=107 Participants	24 Participants n=206 Participants
Age, Continuous	51.9 years STANDARD_DEVIATION 11.8 • n=99 Participants	52.7 years STANDARD_DEVIATION 11.6 • n=107 Participants	52.3 years STANDARD_DEVIATION 11.7 • n=206 Participants
Sex: Female, Male Female	43 Participants n=99 Participants	43 Participants n=107 Participants	86 Participants n=206 Participants
Sex: Female, Male Male	57 Participants n=99 Participants	57 Participants n=107 Participants	114 Participants n=206 Participants
Region of Enrollment United States	90 participants n=99 Participants	81 participants n=107 Participants	171 participants n=206 Participants
Region of Enrollment Canada	7 participants n=99 Participants	15 participants n=107 Participants	22 participants n=206 Participants
Region of Enrollment Australia	3 participants n=99 Participants	3 participants n=107 Participants	6 participants n=206 Participants
Region of Enrollment New Zealand	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants

PRIMARY outcome

Timeframe: Prospective

Population: Intent to Treat Population

Outcome measures

Outcome measures
Measure	hCRF n=100 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=100 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Continue to be Responders at Week 5	57 participants	46 participants

SECONDARY outcome

Timeframe: Prospective

Population: Intent to Treat Population

Outcome measures

Outcome measures
Measure	hCRF n=100 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=100 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Percent of Patients in Each Treatment Group Achieving 50% Reduction in Dexamethasone Usage Relative to Baseline by Week 2 Without Deterioration in Neurological Function as Measured by the 10-Item Neurological Exam and the KPS	78 participants	62 participants

SECONDARY outcome

Timeframe: Prospective

Population: Intent to Treat Population

• The proportion of patients in each treatment group who were Responders at Week 2 and who continued to be Responders at Weeks 5 and 8.

Outcome measures

Outcome measures
Measure	hCRF n=100 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=100 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Who Continue to be Responders at Weeks 5 and 8 Week 2	78 participants	62 participants
The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Who Continue to be Responders at Weeks 5 and 8 Week 5	62 participants	48 participants
The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Who Continue to be Responders at Weeks 5 and 8 Week 8	57 participants	42 participants

SECONDARY outcome

Timeframe: Prospective

Population: Intent to Treat population

Change from Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8, 12 (or Early Study Drug Discontinuation), and 16 (or 4-week follow-up visit). Each item is scored from 0 (normal) to 4 (severely abnormal) except for speech (0-3) for a total range of 0-39. Total score for each patient was the sum of each item score. Change is calculated as the follow-up score minus the baseline score; a negative value indicates improvement.

Outcome measures

Outcome measures
Measure	hCRF n=100 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=100 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation) Week 12	0.1 Scores on a scale Standard Deviation 3.1	0.7 Scores on a scale Standard Deviation 3.4
Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation) Week 2	-0.1 Scores on a scale Standard Deviation 2.3	-0.1 Scores on a scale Standard Deviation 2.7
Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation) Week 5	0.2 Scores on a scale Standard Deviation 2.9	0.4 Scores on a scale Standard Deviation 3.0
Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation) Week 8	0.3 Scores on a scale Standard Deviation 3.1	0.5 Scores on a scale Standard Deviation 3.3
Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation) Last Visit	0.1 Scores on a scale Standard Deviation 3.1	0.8 Scores on a scale Standard Deviation 3.4

SECONDARY outcome

Timeframe: Prospective

Population: Intent to Treat population

Change from Baseline in the Karnofsky Performance Score at Weeks 2, 5, 8, 12 and 16.The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death. Although practitioners occasionally assign performance scores in between standard intervals of 10 as follows: 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment nec

Outcome measures

Outcome measures
Measure	hCRF n=100 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=100 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Change From Baseline in the Karnofsky Performance Score Week 2	-0.5 Scores on a scale Standard Deviation 7.4	-2.2 Scores on a scale Standard Deviation 8.5
Change From Baseline in the Karnofsky Performance Score Week 5	-2.1 Scores on a scale Standard Deviation 9.6	-2.6 Scores on a scale Standard Deviation 8.8
Change From Baseline in the Karnofsky Performance Score Week 8	-3.2 Scores on a scale Standard Deviation 10.3	-3.2 Scores on a scale Standard Deviation 9.0
Change From Baseline in the Karnofsky Performance Score Week 12	-3.4 Scores on a scale Standard Deviation 10.1	-3.3 Scores on a scale Standard Deviation 10.1
Change From Baseline in the Karnofsky Performance Score Last Visit	-3.5 Scores on a scale Standard Deviation 10.1	-3.6 Scores on a scale Standard Deviation 10.2

SECONDARY outcome

Timeframe: Prospective

Population: Intent to Treat; LOCF

The FACT-Br Quality of Life Questionnaire was self-administered at Baseline, Weeks 5 and 12 (or upon Early SDD), and at the post-treatment 4-week follow-up visit (Week 16 and/or any unscheduled 4-week Follow-up).FACT-Br is a reliable and valid 50-item measure that includes FACT-G (27 items) and a brain subscale (23 items) to assess health-related quality of life in brain tumor patients. Each inventory question is scored from 0 (worst possible QOL) to 4 (best possible QOL)

Outcome measures

Outcome measures
Measure	hCRF n=75 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=71 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Change From Baseline in the FACT-Br Quality of Life Results Week 5	0.6 Scores on a scale Standard Deviation 17.5	-2.2 Scores on a scale Standard Deviation 15.8
Change From Baseline in the FACT-Br Quality of Life Results Week 12	-1.8 Scores on a scale Standard Deviation 20.3	-1.9 Scores on a scale Standard Deviation 20.3
Change From Baseline in the FACT-Br Quality of Life Results Week 16	01.7 Scores on a scale Standard Deviation 20.9	-5.9 Scores on a scale Standard Deviation 20.9

SECONDARY outcome

Timeframe: Prospective

Myopathy, using Kendall Myopathy Scale, was assessed at Baseline, Week 12 (or upon Early SDD), and at the post-treatment 4-week follow-up visit (Week 16 and/or any unscheduled 4-week Follow-up). The Kendall Myopathy Scale is a 10 point scale where 10 represents holding test position against strong pressure (best) and 0 represents no contraction palpable (worst).

Outcome measures

Outcome measures
Measure	hCRF n=78 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=77 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Change From Baseline in Myopathy Assessment Results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up Visit) Week 12	0.1 Scores on a scale Standard Deviation 2.8	-0.2 Scores on a scale Standard Deviation 2.2
Change From Baseline in Myopathy Assessment Results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up Visit) Week 16	0.0 Scores on a scale Standard Deviation 2.7	-0.3 Scores on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: Prospective

Population: Intent to Treat population; baseline observation carried forward

The maximum reduction in dexamethasone usage at any time during the study. Dexamethasone dosage was assessed at Weeks 0, 2, 5, 8, 12 and 16.

Outcome measures

Outcome measures
Measure	hCRF n=95 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=92 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Maximum Percent Reduction in Dexamethasone Usage Relative to Baseline Achieved During the Study	-62.7 Percent dexamethasone dose reduction Standard Deviation 21.8	-51.4 Percent dexamethasone dose reduction Standard Deviation 21.5

SECONDARY outcome

Timeframe: Prospective

Population: Intent to Treat population

Numbers of patients who discontinued prior to the Week 5 assessment

Outcome measures

Outcome measures
Measure	hCRF n=100 Participants Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=100 Participants Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Number of Patients Who Discontinued Study Drug Prior to the End of Week 5	29 participants	39 participants

Adverse Events

hCRF

Serious events: 46 serious events

Other events: 99 other events

Deaths: 0 deaths

Placebo

Serious events: 40 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Patrick O'Connor, MD, Managing Director Clinical Development

Celtic Pharma Development Services America Inc

Phone: 212-616-4050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	hCRF n=101 participants at risk Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=99 participants at risk Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Blood and lymphatic system disorders Pancytopenia	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Blood and lymphatic system disorders Anaemia	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Cardiac disorders Myocardial infarction	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Cardiac disorders Arrhythmia	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Eye disorders Blindness	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Eye disorders Glaucoma	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Gastrointestinal disorders Diarrhoea	2.0% 2/101 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Gastrointestinal disorders Ileus paralytic	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Gastrointestinal disorders Peritonitis	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders General physical health deterioration	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Chest pain	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Generalised oedema	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Pyrexia	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Hepatobiliary disorders Biliary colic	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Bacteraemia	2.0% 2/101 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Brain abscess	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Catheter related infection	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Cellulitis	2.0% 2/101 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Herpes zoster	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Meningitis	2.0% 2/101 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Pneumonia	4.0% 4/101 • Number of events 4 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Respiratory Tract infection	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Sepsis	3.0% 3/101 • Number of events 3 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Urosepsis	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Accidental overdose	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Compression fracture	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Fall	2.0% 2/101 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Radiation injury	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Spinal compression fracture	2.0% 2/101 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Traumatic brain injury	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Hyperglycaemia	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Hypokalaemia	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Hyponataemia	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Ketoacidosis	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Metabolic acidosis	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Dehydration	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.99% 1/101 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/101 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.

Other adverse events
Measure	hCRF n=101 participants at risk Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Placebo n=99 participants at risk Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Vascular disorders Flushing	28.7% 29/101 • Number of events 29 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	28.3% 28/99 • Number of events 28 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Nervous system disorders Headache	27.7% 28/101 • Number of events 28 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	28.3% 28/99 • Number of events 28 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Injection site erythema	27.7% 28/101 • Number of events 28 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Oedema peripheral	24.8% 25/101 • Number of events 25 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	21.2% 21/99 • Number of events 21 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	21.8% 22/101 • Number of events 22 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	21.2% 21/99 • Number of events 21 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Fatigue	17.8% 18/101 • Number of events 18 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	29.3% 29/99 • Number of events 29 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Gastrointestinal disorders Nausea	17.8% 18/101 • Number of events 18 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	12.1% 12/99 • Number of events 12 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Musculoskeletal and connective tissue disorders Muscular weakness	15.8% 16/101 • Number of events 16 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	11.1% 11/99 • Number of events 11 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Nervous system disorders Convulsion	13.9% 14/101 • Number of events 14 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	18.2% 18/99 • Number of events 18 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Injection site reaction	13.9% 14/101 • Number of events 14 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Fall	11.9% 12/101 • Number of events 12 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	9.1% 9/99 • Number of events 9 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Gastrointestinal disorders Diarrhoea	11.9% 12/101 • Number of events 12 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	4.0% 4/99 • Number of events 4 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Nervous system disorders Hemiparesis	10.9% 11/101 • Number of events 11 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	3.0% 3/99 • Number of events 3 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Hyperglycaemia	9.9% 10/101 • Number of events 10 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	9.1% 9/99 • Number of events 9 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Psychiatric disorders Insmnia	8.9% 9/101 • Number of events 9 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	11.1% 11/99 • Number of events 11 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Gastrointestinal disorders Vomiting	8.9% 9/101 • Number of events 9 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	9.1% 9/99 • Number of events 9 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Musculoskeletal and connective tissue disorders myopathy	8.9% 9/101 • Number of events 9 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	7.1% 7/99 • Number of events 7 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Psychiatric disorders Confusional state	7.9% 8/101 • Number of events 8 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	11.1% 11/99 • Number of events 11 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Musculoskeletal and connective tissue disorders Back pain	7.9% 8/101 • Number of events 8 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	8.1% 8/99 • Number of events 8 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
General disorders Gait disturbance	7.9% 8/101 • Number of events 8 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	4.0% 4/99 • Number of events 4 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.9% 7/101 • Number of events 7 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	6.1% 6/99 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Skin and subcutaneous tissue disorders Rash	6.9% 7/101 • Number of events 7 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	5.1% 5/99 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Upper respiratory tract infection	6.9% 7/101 • Number of events 7 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	1.0% 1/99 • Number of events 1 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Eye disorders Vision blurred	5.9% 6/101 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	7.1% 7/99 • Number of events 7 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Investigations Weight increased	5.9% 6/101 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	7.1% 7/99 • Number of events 7 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Injury, poisoning and procedural complications Contusion	5.9% 6/101 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	6.1% 6/99 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Urinary tract infection	5.9% 6/101 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	5.1% 5/99 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 6/101 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Nervous system disorders Hypoaesthesia	5.9% 6/101 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Nervous system disorders Tremor	5.9% 6/101 • Number of events 6 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	2.0% 2/99 • Number of events 2 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Psychiatric disorders Depression	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	10.1% 10/99 • Number of events 10 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Nervous system disorders Dizziness	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	9.1% 9/99 • Number of events 9 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Metabolism and nutrition disorders Hypokalaemia	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	5.1% 5/99 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Blood and lymphatic system disorders Thrombocytopenia	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	3.0% 3/99 • Number of events 3 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Gastrointestinal disorders Constipation	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	3.0% 3/99 • Number of events 3 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Pneumonia	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	3.0% 3/99 • Number of events 3 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Vascular disorders Hypertension	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	3.0% 3/99 • Number of events 3 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Infections and infestations Oral candidiasis	5.0% 5/101 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	0.00% 0/99 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Eye disorders Diplopia	4.0% 4/101 • Number of events 4 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	5.1% 5/99 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.
Nervous system disorders Balance disorder	4.0% 4/101 • Number of events 4 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.	5.1% 5/99 • Number of events 5 • Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16 Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.