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

• Sponsor: Celtic Pharma Development Services (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00088166
• Collaborator: Neurobiological Technologies (Industry)
• Enrollment: 200
• Locations: 34
• Arms: 2
• Duration (Months): 46
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of XERECEPT® to dexamethasone (Decadron) a common treatment for symptoms of brain swelling (edema). This study is specifically aimed at patients who require chronic high doses of dexamethasone to manage symptoms.

Condition or Disease	Intervention/Treatment	Phase
Brain Edema; Brain Tumor	Drug: hCRF; Drug: placebo hCRF	Phase 3

Detailed Description

XERECEPT® is not a potential treatment for cancer, but may reduce the edema associated with tumors and as a result, decrease neurological symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Double-Blind, Dexamethasone-Sparing Study Comparing Human Corticotropin-Releasing Factor (hCRF) to Placebo for Control of Symptoms Associated With Peritumoral Brain Edema in Patients With Malignant Brain Tumor Who Require Chronic Administration of High-Dose Dexamethasone
• Study Start Date: May 1, 2004
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Drug: hCRF; hCRF ; open-label dexamethasone that the patient is currently taking; Other Names: XERECEPT (corticorelin acetate injection); hCRF
Placebo Comparator: II Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking	Drug: placebo hCRF; placebo hCRF 2mg/day and open-label dexamethasone that they are taking; Other Names: XERECEPT (corticorelin acetate injection)

Outcome Measures

Primary Outcome Measures

1. The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Continue to be Responders at Week 5 [Prospective]

   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

Secondary Outcome Measures

1. 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 [Prospective]

2. 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 [Prospective]

   • 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.

3. Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation) [Prospective]

   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.

4. Change From Baseline in the Karnofsky Performance Score [Prospective]

   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

5. Change From Baseline in the FACT-Br Quality of Life Results [Prospective]

   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)

6. Change From Baseline in Myopathy Assessment Results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up Visit) [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).

7. Maximum Percent Reduction in Dexamethasone Usage Relative to Baseline Achieved During the Study [Prospective]

   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.

8. Number of Patients Who Discontinued Study Drug Prior to the End of Week 5 [Prospective]

   Numbers of patients who discontinued prior to the Week 5 assessment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed diagnosis of a primary malignant brain tumor or, if metastatic, documentation and histology (if available) of primary source of cancer.

• Patient must have 1 or more qualifying steroid-associated side effect(s) at Baseline.

• Patient has required administration of dexamethasone to control symptoms of peritumoral edema for at least 30 days.

• Stable dexamethasone dose of 4-24 mg/day for at least 14 days prior to Baseline.

• Need for administration of dexamethasone to treat peritumoral brain edema (referenced above) has been documented by MRI or comparable diagnostic technology within 21 days of Baseline.

• Karnofsky score of > 50 at Screening and Baseline.

• Capable of self-administration of subcutaneous injections twice daily for 12 weeks, or availability of assistance from caregiver.

• Ability to provide written informed consent or, if unable to provide, have a legal guardian or representative provide written informed consent.

• For women of childbearing potential: a negative serum pregnancy test at Screening.

• Must be 18 years of age or older

Exclusion Criteria:

• Ongoing or anticipated need for surgery, radiosurgery or radiation therapy or the introduction of new chemotherapeutic regime within the first 5 weeks of study enrollment. Treatment with pre-study chemotherapy may continue.

• Concurrent enrollment in any other investigational drug or device study, or plan to enroll in such a study during the first 5 weeks of treatment.

• Systemic steroid use for any indication other than peritumoral brain edema.

• Use or intended use of dexamethasone as an anti-emetic during Screening or Study

• Non-compliance with dexamethasone or anticonvulsant therapy.

• Clinical signs and symptoms of cerebral herniation.

• Serious concomitant cardiovascular, pulmonary, renal, gastrointestinal or endocrine metabolic disease which could put the patient at unusual risk for study participation.

• Confounding previous or concurrent neurological disorders that would interfere with adequate clinical evaluation.

• Clinically significant head injury or chronic seizure disorder, if the condition results in functional impairment or is likely to interfere with evaluations. (Maintenance anticonvulsant therapy is allowed.)

• Central nervous system infection.

• Pregnancy, breastfeeding and/or refusal to practice birth control while in study, for women of childbearing potential.

• Any conditions that are considered contraindications for patients to receive niacin, e.g. liver disease (with LFTs > 3 times the upper limit of the norm),active peptic ulcer, arterial hemorrhage, asthma and known hypersensitivity to niacin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
2	UCSF Fresno Center for Clinical Studies	Fresno	California	United States	93702
3	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92658
4	Stanford University Medical Center	Palo Alto	California	United States	94305
5	UC Davis Medical Center, Division of Medical Oncology	Sacramento	California	United States	95817
6	UC San Diego, Thornton Hospital	San Diego	California	United States	92037
7	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
8	Colorado Neurological Institute	Englewood	Colorado	United States	80113
9	Mayo Clinic	Jacksonville	Florida	United States	32224
10	Cancer Institute of Orlando	Orlando	Florida	United States	32804
11	Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612-9497
12	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
13	Northwestern University, Feinberg School of Medicine	Chicago	Illinois	United States	60611
14	Evanston Northwestern Healthcare	Evanston	Illinois	United States	60201
15	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
16	Hermelin Brain Tumor Center, Henry Ford Hospital	Detroit	Michigan	United States	48202
17	Neurology Group of Bergen County	Ridgewood	New Jersey	United States	07450
18	Dent Neurologic Institute	Amherst	New York	United States	14226
19	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
20	Weill Medical College of Cornell University	New York	New York	United States	10021
21	University Hematology Oncology Care, LLC	Cincinnati	Ohio	United States	43210
22	Good Samaritan Hospital	Cincinnati	Ohio	United States	45220
23	The Ohio State University	Columbus	Ohio	United States	43210
24	Oregon Clinic	Portland	Oregon	United States	97210
25	Virginia Mason Clinic	Seattle	Washington	United States	98111
26	University of Wisconsin	Madison	Wisconsin	United States	53792
27	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226-3596
28	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G1ZT
29	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
30	The Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
31	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 1V7
32	Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
33	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K1H 1C4
34	Sunnybrook and Women's College Health	Toronto	Ontario	Canada	M4N 3M5

Sponsors and Collaborators

• Celtic Pharma Development Services
• Neurobiological Technologies

Investigators

• Principal Investigator: William Shapiro, MD, Barrow Neurological Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celtic Pharma Development Services
• ClinicalTrials.gov Identifier: NCT00088166
• Other Study ID Numbers: NTI 0303; XERECEPT®; NCT00091013
• First Posted: Jul 22, 2004
• Last Update Posted: Aug 13, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Celtic Pharma Development Services: peritumoral brain edema; edema; malignant brain tumor; astrocytoma; brain tumor; dexamethasone; Decadron
• Additional relevant MeSH terms: Brain Neoplasms; Brain Edema; Edema; Corticotropin-Releasing Hormone

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	hCRF	Placebo	Total
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking	Total of all reporting groups
Overall Participants	100	100	200
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	89 89%	87 87%	176 88%
>=65 years	11 11%	13 13%	24 12%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (11.8)	52.7 (11.6)	52.3 (11.7)
Sex: Female, Male (Count of Participants)
Female	43 43%	43 43%	86 43%
Male	57 57%	57 57%	114 57%
Region of Enrollment (participants) [Number]
United States	90 90%	81 81%	171 85.5%
Canada	7 7%	15 15%	22 11%
Australia	3 3%	3 3%	6 3%
New Zealand	0 0%	1 1%	1 0.5%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Continue to be Responders at Week 5
Description	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
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	100	100
Number [participants]	57 57%	46 46%

2. Secondary Outcome

Title	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
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	100	100
Number [participants]	78 78%	62 62%

3. Secondary Outcome

Title	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
Description	• 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.
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	100	100
Week 2	78 78%	62 62%
Week 5	62 62%	48 48%
Week 8	57 57%	42 42%

4. Secondary Outcome

Title	Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation)
Description	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.
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat population

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	100	100
Week 2	-0.1 (2.3)	-0.1 (2.7)
Week 5	0.2 (2.9)	0.4 (3.0)
Week 8	0.3 (3.1)	0.5 (3.3)
Week 12	0.1 (3.1)	0.7 (3.4)
Last Visit	0.1 (3.1)	0.8 (3.4)

5. Secondary Outcome

Title	Change From Baseline in the Karnofsky Performance Score
Description	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
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat population

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	100	100
Week 2	-0.5 (7.4)	-2.2 (8.5)
Week 5	-2.1 (9.6)	-2.6 (8.8)
Week 8	-3.2 (10.3)	-3.2 (9.0)
Week 12	-3.4 (10.1)	-3.3 (10.1)
Last Visit	-3.5 (10.1)	-3.6 (10.2)

6. Secondary Outcome

Title	Change From Baseline in the FACT-Br Quality of Life Results
Description	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)
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat; LOCF

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	75	71
Week 5	0.6 (17.5)	-2.2 (15.8)
Week 12	-1.8 (20.3)	-1.9 (20.3)
Week 16	01.7 (20.9)	-5.9 (20.9)

7. Secondary Outcome

Title	Change From Baseline in Myopathy Assessment Results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up Visit)
Description	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).
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	78	77
Week 12	0.1 (2.8)	-0.2 (2.2)
Week 16	0.0 (2.7)	-0.3 (2.5)

8. Secondary Outcome

Title	Maximum Percent Reduction in Dexamethasone Usage Relative to Baseline Achieved During the Study
Description	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.
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat population; baseline observation carried forward

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	95	92
Mean (Standard Deviation) [Percent dexamethasone dose reduction]	-62.7 (21.8)	-51.4 (21.5)

9. Secondary Outcome

Title	Number of Patients Who Discontinued Study Drug Prior to the End of Week 5
Description	Numbers of patients who discontinued prior to the Week 5 assessment
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat population

Arm/Group Title	hCRF	Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.	Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
Measure Participants	100	100
Number [participants]	29 29%	39 39%

Adverse Events

Time Frame	Treatment emergent adverse events (TEAEs) were reported at each visit to Week 16
Adverse Event Reporting Description	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.
Arm/Group Title	hCRF		Placebo
Arm/Group Description	Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.		Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
All Cause Mortality
	hCRF		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	hCRF		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/101 (45.5%)		40/99 (40.4%)
Blood and lymphatic system disorders
Heparin-induced thrombocytopenia	1/101 (1%)	1	0/99 (0%)	0
Pancytopenia	1/101 (1%)	1	0/99 (0%)	0
Anaemia	0/101 (0%)	0	2/99 (2%)	2
Cardiac disorders
Myocardial infarction	1/101 (1%)	1	0/99 (0%)	0
Arrhythmia	0/101 (0%)	0	1/99 (1%)	1
Eye disorders
Blindness	0/101 (0%)	0	1/99 (1%)	1
Glaucoma	0/101 (0%)	0	1/99 (1%)	1
Gastrointestinal disorders
Diarrhoea	2/101 (2%)	2	0/99 (0%)	0
Ileus paralytic	0/101 (0%)	0	1/99 (1%)	1
Peritonitis	0/101 (0%)	0	1/99 (1%)	1
General disorders
General physical health deterioration	1/101 (1%)	1	1/99 (1%)	1
Chest pain	0/101 (0%)	0	1/99 (1%)	1
Generalised oedema	0/101 (0%)	0	1/99 (1%)	1
Pyrexia	0/101 (0%)	0	2/99 (2%)	2
Hepatobiliary disorders
Biliary colic	1/101 (1%)	1	0/99 (0%)	0
Infections and infestations
Bacteraemia	2/101 (2%)	2	0/99 (0%)	0
Brain abscess	1/101 (1%)	1	1/99 (1%)	1
Catheter related infection	0/101 (0%)	0	2/99 (2%)	2
Cellulitis	2/101 (2%)	2	2/99 (2%)	2
Herpes zoster	1/101 (1%)	1	0/99 (0%)	0
Meningitis	2/101 (2%)	2	1/99 (1%)	1
Pneumonia	4/101 (4%)	4	2/99 (2%)	2
Respiratory Tract infection	0/101 (0%)	0	1/99 (1%)	1
Sepsis	3/101 (3%)	3	1/99 (1%)	1
Urosepsis	1/101 (1%)	1	0/99 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/101 (1%)	1	0/99 (0%)	0
Cervical vertebral fracture	1/101 (1%)	1	0/99 (0%)	0
Compression fracture	1/101 (1%)	1	0/99 (0%)	0
Fall	2/101 (2%)	2	1/99 (1%)	1
Radiation injury	1/101 (1%)	1	0/99 (0%)	0
Spinal compression fracture	2/101 (2%)	2	1/99 (1%)	1
Traumatic brain injury	1/101 (1%)	1	0/99 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	1/101 (1%)	1	0/99 (0%)	0
Hypokalaemia	1/101 (1%)	1	0/99 (0%)	0
Hyponataemia	1/101 (1%)	1	0/99 (0%)	0
Ketoacidosis	1/101 (1%)	1	0/99 (0%)	0
Metabolic acidosis	1/101 (1%)	1	0/99 (0%)	0
Dehydration	0/101 (0%)	0	1/99 (1%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/101 (1%)	1	0/99 (0%)	0
Back pain	0/101 (0%)	0	1/99 (1%)	1
Muscular weakness	0/101 (0%)	0	3/99 (3%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic	1/101 (1%)	1	1/99 (1%)	1
Glioblastoma multiforme	1/101 (1%)	1	0/99 (0%)	0
Large cell carcinoma respiratory tract	1/101 (1%)	1	0/99 (0%)	0
Lung neoplasm malignant	0/101 (0%)	0	1/99 (1%)	1
Metastases to meninges	0/101 (0%)	0	1/99 (1%)	1
Metastatic neoplasm	0/101 (0%)	0	1/99 (1%)	1
Neoplasm progression	15/101 (14.9%)	15	19/99 (19.2%)	19
Non-small cell lung cancer	0/101 (0%)	0	1/99 (1%)	1
Nervous system disorders
Ataxia	1/101 (1%)	1	0/99 (0%)	0
Brain oedema	1/101 (1%)	1	3/99 (3%)	3
Convulsion	7/101 (6.9%)	7	5/99 (5.1%)	5
Cerebral haemorrhage	0/101 (0%)	0	2/99 (2%)	2
Cerebral schaemia	0/101 (0%)	0	1/99 (1%)	1
Grand mal convulsion	1/101 (1%)	1	0/99 (0%)	0
Headache	1/101 (1%)	1	0/99 (0%)	0
Hydrocephalus	1/101 (1%)	1	1/99 (1%)	1
Hemiparesis	2/101 (2%)	2	0/99 (0%)	0
Intracranial hypotension	0/101 (0%)	0	1/99 (1%)	1
Metabolic encephalopathy	1/101 (1%)	1	0/99 (0%)	0
Partial seizures	1/101 (1%)	1	0/99 (0%)	0
Somnolence	0/101 (0%)	0	1/99 (1%)	1
Syncope	1/101 (1%)	1	0/99 (0%)	0
Psychiatric disorders
Mental disorder	1/101 (1%)	1	0/99 (0%)	0
Mental status changes	2/101 (2%)	2	0/99 (0%)	0
Renal and urinary disorders
Renal failure	0/101 (0%)	0	1/99 (1%)	1
Renal failure acute	0/101 (0%)	0	2/99 (2%)	2
Respiratory, thoracic and mediastinal disorders
Aspiration	1/101 (1%)	1	0/99 (0%)	0
COPD	0/101 (0%)	0	1/99 (1%)	1
Dyspnoea	0/101 (0%)	0	1/99 (1%)	1
Hypoxia	0/101 (0%)	0	1/99 (1%)	1
Pneumonia aspiration	1/101 (1%)	1	1/99 (1%)	1
Pneumonitis	0/101 (0%)	0	1/99 (1%)	1
Pulmonary embolism	3/101 (3%)	3	6/99 (6.1%)	6
Respiratory depression	1/101 (1%)	1	0/99 (0%)	0
Respiratory distress	1/101 (1%)	1	0/99 (0%)	0
Respiratory failure	1/101 (1%)	1	1/99 (1%)	1
Haemoptysis	0/101 (0%)	0	1/99 (1%)	1
Skin and subcutaneous tissue disorders
Erythema	1/101 (1%)	1	0/99 (0%)	0
Swelling face	1/101 (1%)	1	0/99 (0%)	0
Pruritis	0/101 (0%)	0	1/99 (1%)	1
Rash	0/101 (0%)	0	1/99 (1%)	1
Vascular disorders
Venous thrombosis limb	1/101 (1%)	1	0/99 (0%)	0
Deep vein thrombosis	0/101 (0%)	0	3/99 (3%)	3
Other (Not Including Serious) Adverse Events
	hCRF		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/101 (98%)		97/99 (98%)
Blood and lymphatic system disorders
Thrombocytopenia	5/101 (5%)	5	3/99 (3%)	3
Endocrine disorders
Cushingoid	2/101 (2%)	2	13/99 (13.1%)	13
Eye disorders
Vision blurred	6/101 (5.9%)	6	7/99 (7.1%)	7
Diplopia	4/101 (4%)	4	5/99 (5.1%)	5
Gastrointestinal disorders
Nausea	18/101 (17.8%)	18	12/99 (12.1%)	12
Diarrhoea	12/101 (11.9%)	12	4/99 (4%)	4
Vomiting	9/101 (8.9%)	9	9/99 (9.1%)	9
Constipation	5/101 (5%)	5	3/99 (3%)	3
General disorders
Injection site erythema	28/101 (27.7%)	28	1/99 (1%)	1
Oedema peripheral	25/101 (24.8%)	25	21/99 (21.2%)	21
Fatigue	18/101 (17.8%)	18	29/99 (29.3%)	29
Injection site reaction	14/101 (13.9%)	14	0/99 (0%)	0
Gait disturbance	8/101 (7.9%)	8	4/99 (4%)	4
Pyrexia	2/101 (2%)	2	5/99 (5.1%)	5
Infections and infestations
Upper respiratory tract infection	7/101 (6.9%)	7	1/99 (1%)	1
Urinary tract infection	6/101 (5.9%)	6	5/99 (5.1%)	5
Pneumonia	5/101 (5%)	5	3/99 (3%)	3
Oral candidiasis	5/101 (5%)	5	0/99 (0%)	0
Candidiasis	1/101 (1%)	1	6/99 (6.1%)	6
Injury, poisoning and procedural complications
Fall	12/101 (11.9%)	12	9/99 (9.1%)	9
Contusion	6/101 (5.9%)	6	6/99 (6.1%)	6
Investigations
Weight increased	6/101 (5.9%)	6	7/99 (7.1%)	7
Metabolism and nutrition disorders
Hyperglycaemia	10/101 (9.9%)	10	9/99 (9.1%)	9
Hypokalaemia	5/101 (5%)	5	5/99 (5.1%)	5
Musculoskeletal and connective tissue disorders
Muscular weakness	16/101 (15.8%)	16	11/99 (11.1%)	11
myopathy	9/101 (8.9%)	9	7/99 (7.1%)	7
Back pain	8/101 (7.9%)	8	8/99 (8.1%)	8
Arthralgia	6/101 (5.9%)	6	2/99 (2%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	22/101 (21.8%)	22	21/99 (21.2%)	21
Nervous system disorders
Headache	28/101 (27.7%)	28	28/99 (28.3%)	28
Convulsion	14/101 (13.9%)	14	18/99 (18.2%)	18
Hemiparesis	11/101 (10.9%)	11	3/99 (3%)	3
Hypoaesthesia	6/101 (5.9%)	6	2/99 (2%)	2
Tremor	6/101 (5.9%)	6	2/99 (2%)	2
Dizziness	5/101 (5%)	5	9/99 (9.1%)	9
Balance disorder	4/101 (4%)	4	5/99 (5.1%)	5
Aphasia	3/101 (3%)	3	7/99 (7.1%)	7
Partial seizures	3/101 (3%)	3	7/99 (7.1%)	7
Ataxia	3/101 (3%)	3	6/99 (6.1%)	6
Somnolence	3/101 (3%)	3	5/99 (5.1%)	5
Brain oedema	2/101 (2%)	2	5/99 (5.1%)	5
Cognitive disorder	1/101 (1%)	1	5/99 (5.1%)	5
Psychiatric disorders
Insmnia	9/101 (8.9%)	9	11/99 (11.1%)	11
Confusional state	8/101 (7.9%)	8	11/99 (11.1%)	11
Depression	5/101 (5%)	5	10/99 (10.1%)	10
Respiratory, thoracic and mediastinal disorders
Dyspnoea	7/101 (6.9%)	7	6/99 (6.1%)	6
Cough	3/101 (3%)	3	7/99 (7.1%)	7
Pulmonary embolism	3/101 (3%)	3	6/99 (6.1%)	6
Skin and subcutaneous tissue disorders
Rash	7/101 (6.9%)	7	5/99 (5.1%)	5
Vascular disorders
Flushing	29/101 (28.7%)	29	28/99 (28.3%)	28
Hypertension	5/101 (5%)	5	3/99 (3%)	3
Deep vein thrombosis	2/101 (2%)	2	6/99 (6.1%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.