CMX001 in Post-transplant Patients With BK Virus Viruria

• Sponsor: Chimerix (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00793598
• Collaborator: (none)
• Enrollment: 29
• Locations: 15
• Arms: 2
• Actual Duration (Months): 11
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This was a randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus viruria.

Condition or Disease	Intervention/Treatment	Phase
Viruria	Drug: Placebo; Drug: Brincidofovir	Phase 1/Phase 2

Detailed Description

This was a randomized, double-blind, multiple-dose placebo-controlled study of oral brincidofovir (BCV) in hematopoietic stem cell transplant and renal transplant recipients with BK virus infection.

Subjects received blinded study medication for a total of 5 doses in 1 of the following regimens:

• 10 mg BCV administered twice weekly (BIW) on Days 0, 3, 7, 10, 14.

• 20 mg BCV administered once weekly (QW) on Days 0, 7, and 14 and placebo administered on Days 3 or 10.

• Placebo administered BIW on Days 0, 3, 7, 10 ,14.

• 40 mg BCV administered QW on Days 0, 7, 14, 21, and 28.

• Placebo administered QW on Days 0, 7, 14, 21, and 28.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of the Safety, Tolerability and Population Pharmacokinetics of CMX001 in Post-Transplant Subjects With BK Virus Viruria
• Actual Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brincidofovir Under Amendments 1 and 2, subjects received 1 of 2 dose regimens of brincidofovir, as follows: 20 mg BCV once weekly (QW) on Days 0, 7, and 14; or 10 mg BCV twice weekly (BIW) BIW on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received 40 mg BCV QW for a total of 5 doses on Days 0, 7, 14, 21, and 28.	Drug: Brincidofovir; Other Names: BCV CMX001
Placebo Comparator: Placebo Under Amendments 1 and 2, subjects received placebo twice weekly (BIW) for a total of 5 doses on Days 0, 3, 7, 10, and 14. Under Amendment 3, subjects received placebo once weekly (QW) for a total of 5 doses on Days 0, 7, 14, 21, and 28.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events in Post-Transplant Patients With BK Virus Viruria [35 days (Day 0 to Day 35)]

   The primary objective of this study was to determine the safety and tolerability of brincidofovir (BCV) in post-transplant patients with BK virus viruria. Safety measures included adverse events, clinical laboratory values, vital signs, and renal and gastrointestinal function.

Secondary Outcome Measures

1. Percentage of Patients Who Achieved BK Viruria Resolution [28 days]

   The percentage of subjects who cleared the virus was calculated. Concentrations below the lower limit of quantification were indicated as below the limit of quantitation and were considered "cleared".

2. Number of Patients Who Achieved a Clinically Significant Decrease in BK Viruria [28 days]

   A 2-log drop in viruria or viremia or clearance of virus was considered significant. Percentages of subjects with a 2-log drop in viral load were calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

For inclusion into the trial, subjects were required to fulfill all of the following criteria:

1. Aged between 18 to 75 years, inclusive. Males must have been able and willing to use adequate contraceptive methods throughout the study and for 3 months after the final dose. Females must have been post-menopausal, surgically sterile, or willing to use adequate contraception for the duration of the study (screening through the Day 48 visit).

2. Were renal or hematopoietic stem cell transplant patients who met the following criteria:

3. Renal transplant patients who:

• Were at least 28 days post transplant;

• Were in stable condition with hemoglobin >10 g/100 mL;

• Had no evidence of graft rejection (i.e., serum creatinine was not increasing [±30%], creatinine clearance was not decreasing);

• Were on a stable immunosuppressant regimen for at least 14 days prior to dosing.

• Had either urine levels of BK virus DNA ≥10^{4 copies/mL without viremia or plasma levels of BK virus DNA <10}4 copies/mL (with or without viruria).

1. Stem cell transplant patients who:

• Were a minimum of 3 days post documentation of successful engraftment as evidenced by an absolute neutrophil count >500 cells/mm3;

• Had urine levels of BKV ≥10^4 copies/mL.

1. Had GFR >30 mL/min.

2. Were able to swallow tablets.

3. Were willing and able to understand and provide written informed consent.

4. Were willing and able to participate in all required study activities for the duration of the study (including ingestion of oral medication).

Exclusion Criteria

Any of the following was regarded as a criterion for exclusion from the trial:

1. Females who were currently nursing or pregnant.

2. Were using illicit drugs or abusing alcohol.

3. Had hypersensitivity to cidofovir or brincidofovir.

4. Had received aminoglycosides (intravenously) or NSAIDS (except as given for cardioprotective treatment) within 7 days prior to enrollment; had received leflunomide, cidofovir, or any other medication for treatment of BK virus infection or disease within 14 days prior to enrollment; had received any investigational drug (including maribavir) within 30 days prior to enrollment.

5. Were HIV positive (results must have been obtained within 1 year prior to dosing); had active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.

6. Were renal transplant patients with evidence of biopsy proven acute rejection in the 3 weeks prior to enrollment. This exclusion criterion applied only to those patients for whom a biopsy was performed within the 3 weeks prior to enrollment.

7. Were stem cell transplant patients who:

8. Had cystitis ≥Grade 3 National Cancer Institute, Common Terminology Criteria for Adverse Events version 3.0.

9. Had Grade 3 or 4 graft versus host disease (GVHD).

10. Had untreated or uncontrolled Grade 2 GVHD.

11. Had received ganciclovir or valganciclovir within 14 days prior to enrollment.

12. Had mucositis that prevented ingestion of oral medication.

13. Had hypotony, uveitis, or retinitis or any intraocular pathology that would have predisposed the patient to any one of these conditions.

14. Had unstable or poorly controlled diabetes, defined as having frequent hypoglycemic and/or hyperglycemic events on a daily basis (brittle diabetes), with fluctuating short acting insulin requirements daily, or requiring unpredictable insulin supplementation to oral hypoglycemic agents on a regular basis.

15. Had bilirubin >2.5 x the upper limit of normal.

16. Had cardiovascular disease which, in the opinion of the investigator, would have interfered with the conduct of the study.

17. Had any of the following autoimmune diseases: Addison's disease, autoimmune hemolytic anemia, autoimmune hepatitis, bullous pemphigoid, celiac disease, dermatomyositis, active Goodpasture's syndrome, idiopathic thrombocytopenic purpura, active lupus erythematosus, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, polymyositis, primary biliary cirrhosis, vasculitis, Wegener's granulomatosis.

18. Had active malignancies (with the exception of basal cell carcinoma or the condition under treatment for hematopoietic stem cell transplant patients).

19. Had concurrent or ongoing ≥Grade 2 gastrointestinal symptoms including nausea, vomiting, diarrhea, constipation, or gastroenteritis. Patients with active gastrointestinal disease including inflammatory bowel disease, irritable bowel syndrome, or celiac sprue.

20. Had any other condition including abnormal laboratory values that would have, in the judgement of the investigator, put the subject at increased risk for participating in the trial, or interfered with the conduct of the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Pacific Medical Center	San Francisco	California	United States	94115
2	University of California, San Francisco	San Francisco	California	United States	94143-0780
3	Northwestern University	Chicago	Illinois	United States	60611
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	Tulane Center for Abdominal Transplant	New Orleans	Louisiana	United States	70112
6	Johns Hopkins Medical Institutions	Baltimore	Maryland	United States	21287
7	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
8	University of Michigan	Ann Arbor	Michigan	United States	48109
9	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
10	Mt. Sinai Medical Center	New York	New York	United States	10029
11	UNC Kidney Center	Chapel Hill	North Carolina	United States	27599
12	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
13	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15260
14	University of Vermont	Burlington	Vermont	United States	05405
15	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	19024

Sponsors and Collaborators

• Chimerix

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chimerix
• ClinicalTrials.gov Identifier: NCT00793598
• Other Study ID Numbers: CMX001-104
• First Posted: Nov 19, 2008
• Last Update Posted: Aug 16, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Chimerix: CMX001; Kidney transplant; HSCT transplant; BK Virus; Post kidney transplant patients with BK virus viruria > 10^4; Post HSCT transplant patients with BK virus viruria > 10^4
• Additional relevant MeSH terms: Brincidofovir

Study Results

Participant Flow

Pre-assignment Detail	1 HCT subject in the 40 mg BCV QW treatment arm was not dosed with BCV and, therefore, is not included in further analyses.

Arm/Group Title	10 mg BCV BIW RT	10 mg BCV BIW HCT	20 mg BCV QW HCT	Placebo BIW HCT	40 mg BCV QW RT	40 mg BCV QW HCT	Placebo QW RT	Placebo QW HCT
Arm/Group Description	Renal transplant (RT) recipients who received 10 mg brincidofovir (BCV) administered twice weekly (BIW) on Days 0, 3, 7, 10, and 14.	Hematopoietic stem cell transplant (HCT) recipients who received 10 mg brincidofovir (BCV) administered twice weekly (BIW) on Days 0, 3, 7, 10, and 14.	Hematopoietic stem cell transplant (HCT) recipients who received 20 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, and 14.	Hematopoietic stem cell transplant (HCT) recipients who received placebo twice weekly (BIW) under Amendment 2.	Renal transplant (RT) recipients who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.	Hematopoietic stem cell transplant (HCT) recipients who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.	Renal transplant (RT) recipients who received placebo once weekly (QW) under Amendment 3.	Hematopoietic stem cell transplant (HCT) recipients who received placebo once weekly (QW) under Amendment 3.
Period Title: Overall Study
STARTED	1	1	1	2	8	8	4	4
COMPLETED	1	0	1	2	8	7	4	3
NOT COMPLETED	0	1	0	0	0	1	0	1

Baseline Characteristics

Arm/Group Title	10 mg BCV BIW	20 mg BCV QW	Placebo BIW	40 mg BCV QW	Placebo QW	Total
Arm/Group Description	Subjects who received 10 mg brincidofovir (BCV) administered twice weekly (BIW) on Days 0, 3, 7, 10, and 14.	Subjects who received 20 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, and 14.	Subjects who received placebo twice weekly (BIW) under Amendment 2.	Subjects who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0 7, 14, 21, and 28.	Subjects who received placebo once weekly (QW) under Amendment 3.	Total of all reporting groups
Overall Participants	2	1	2	15	8	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40 (10)	60 (0)	60 (2)	55.5 (15.14)	51.0 (10.46)	51.5 (14.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	1 50%	3 20%	4 50%	8 28.6%
Male	2 100%	1 100%	1 50%	12 80%	4 50%	20 71.4%
Type of transplant received (Count of Participants)
Hematopoietic stem cell transplant recipients	1 50%	1 100%	2 100%	7 46.7%	4 50%	15 53.6%
Renal transplant recipients	1 50%	0 0%	0 0%	8 53.3%	4 50%	13 46.4%

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events in Post-Transplant Patients With BK Virus Viruria
Description	The primary objective of this study was to determine the safety and tolerability of brincidofovir (BCV) in post-transplant patients with BK virus viruria. Safety measures included adverse events, clinical laboratory values, vital signs, and renal and gastrointestinal function.
Time Frame	35 days (Day 0 to Day 35)

Outcome Measure Data

Analysis Population Description

1 subject in the 40 mg BCV QW HCT treatment arm was not dosed with BCV and, therefore, was not included in this analysis.

Arm/Group Title	10 mg BCV BIW RT	10 mg BCV BIW HCT	20 mg BCV BIW HCT	Placebo BIW HCT	40 mg BCV QW RT	40 mg BCV QW HCT	Placebo QW RT	Placebo QW HCT
Arm/Group Description	Renal transplant (RT) recipients who received 10 mg brincidofovir (BCV) administered twice weekly	Hematopoietic stem cell transplant (HCT) recipients who received 10 mg brincidofovir (BCV) administered twice weekly (BIW) on Days 0, 3, 7, 10, and 14.	Hematopoietic stem cell transplant (HCT) recipients who received 20 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, and 14.	Hematopoietic stem cell transplant (HCT) recipients who received placebo twice weekly (BIW) under Amendment 2.	Renal transplant (RT) recipients who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.	Hematopoietic stem cell transplant (HCT) recipients who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.	Renal transplant (RT) recipients who received placebo once weekly (QW) under Amendment 3.	Hematopoietic stem cell transplant (HCT) recipients who received placebo once weekly (QW) under Amendment 3.
Measure Participants	1	1	1	2	8	7	4	4
Subjects who experienced at least 1 an adverse event	1 50%	1 100%	1 50%	2 13.3%	8 100%	7 25%	3 NaN	4 NaN
Subjects who did not experience an adverse event	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 NaN	0 NaN

2. Secondary Outcome

Title	Percentage of Patients Who Achieved BK Viruria Resolution
Description	The percentage of subjects who cleared the virus was calculated. Concentrations below the lower limit of quantification were indicated as below the limit of quantitation and were considered "cleared".
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Hematopoietic stem cell (HCT) recipients and renal transplant (RT) recipients enrolled under Amendment 3 who had detectable BK viruria at baseline (Day 0). 1 HCT subject in the 40 mg BCV QW treatment arm was not dosed with BCV and, therefore, is not included in this analysis.

Arm/Group Title	40 mg BCV QW	Placebo
Arm/Group Description	Subjects who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.	Subjects who received placebo once weekly (QW) on Days 0, 7, 14, 21 and 28.
Measure Participants	15	8
Subjects who cleared viruria	1 50%	0 0%
Subjects who did not clear viruria	6 300%	4 400%
Subjects who cleared viruria	1 50%	0 0%
Subjects who did not clear viruria	7 350%	4 400%

3. Secondary Outcome

Title	Number of Patients Who Achieved a Clinically Significant Decrease in BK Viruria
Description	A 2-log drop in viruria or viremia or clearance of virus was considered significant. Percentages of subjects with a 2-log drop in viral load were calculated.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Hematopoietic stem cell (HCT) recipients and renal transplant (RT) recipients enrolled under Amendment 3 who had detectable BK viruria at baseline (Day 0). 1 HCT subject in the 40 mg BCV QW treatment arm was not dosed with BCV and, therefore, is not included in this analysis.

Arm/Group Title	40 mg BCV QW	Placebo QW
Arm/Group Description	Subjects randomized to receive 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.	Subjects who received placebo once weekly (QW) on Days 0, 7, 14, 21 and 28.
Measure Participants	15	8
Subjects with 2-log drop from Day 0	1 50%	1 100%
Subjects without 2-log drop from Day 0	6 300%	3 300%
Subjects with 2-log drop from Day 0	0 0%	0 0%
Subjects without 2-log drop from Day 0	8 400%	4 400%

Adverse Events

Time Frame	Day 0 to Day 35
Adverse Event Reporting Description	1 HCT subject in the 40 mg BCV QW treatment arm was not dosed with BCV and, therefore, is not included in this analysis.
Arm/Group Title	10 mg BCV BIW RT		10 mg BCV BIW HCT		20 mg BCV QW HCT		Placebo BIW HCT		40 mg BCV QW RT		40 mg BCV QW HCT		Placebo QW RT		Placebo QW HCT
Arm/Group Description	Renal transplant (RT) recipients who received 10 mg brincidofovir (BCV) administered twice weekly (BIW) on Days 0, 3, 7, 10, and 14.		Hematopoietic stem cell transplant (HCT) recipients who received 10 mg brincidofovir (BCV) administered twice weekly (BIW) on Days 0, 3, 7, 10, and 14.		Hematopoietic stem cell transplant (HCT) recipients who received 20 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, and 14.		Hematopoietic stem cell transplant (HCT) recipients who received placebo twice weekly (BIW) under Amendment 2.		Renal transplant (RT) recipients who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.		Hematopoietic stem cell transplant (HCT) recipients who received 40 mg brincidofovir (BCV) administered once weekly (QW) on Days 0, 7, 14, 21, and 28.		Renal transplant (RT) recipients who received placebo once weekly (QW) under Amendment 3.		Hematopoietic stem cell transplant (HCT) recipients who received placebo once weekly (QW) under Amendment 3.
All Cause Mortality
	10 mg BCV BIW RT		10 mg BCV BIW HCT		20 mg BCV QW HCT		Placebo BIW HCT		40 mg BCV QW RT		40 mg BCV QW HCT		Placebo QW RT		Placebo QW HCT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	10 mg BCV BIW RT		10 mg BCV BIW HCT		20 mg BCV QW HCT		Placebo BIW HCT		40 mg BCV QW RT		40 mg BCV QW HCT		Placebo QW RT		Placebo QW HCT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		2/7 (28.6%)		0/4 (0%)		1/4 (25%)
Blood and lymphatic system disorders
Methemoglobinemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
General disorders
Pyrexia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Immune system disorders
Acute graft versus host disease skin	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Acute graft versus host disease in intestine	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Pancreas transplant rejection	1/1 (100%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Infections and infestations
Pneumonia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Renal and urinary disorders
Haematuria	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Oliguria	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	10 mg BCV BIW RT		10 mg BCV BIW HCT		20 mg BCV QW HCT		Placebo BIW HCT		40 mg BCV QW RT		40 mg BCV QW HCT		Placebo QW RT		Placebo QW HCT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		1/1 (100%)		2/2 (100%)		8/8 (100%)		7/7 (100%)		3/4 (75%)		4/4 (100%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		2/4 (50%)
Leukopenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		2/4 (50%)
Neutropenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		2/4 (50%)
Cardiac disorders
Sinus tachycardia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Ear and labyrinth disorders
Ear pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		1/4 (25%)		1/4 (25%)
Endocrine disorders
Adrenal insufficiency	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Androgen deficiency	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Eye disorders
Eye haemorrhage	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		1/4 (25%)		0/4 (0%)
Vision blurred	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		2/7 (28.6%)		0/4 (0%)		0/4 (0%)
Abdominal pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Constipation	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Diarrhoea	0/1 (0%)		1/1 (100%)		0/1 (0%)		0/2 (0%)		3/8 (37.5%)		2/7 (28.6%)		0/4 (0%)		2/4 (50%)
Flatulence	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		2/7 (28.6%)		0/4 (0%)		0/4 (0%)
Gingival pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Nausea	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		1/8 (12.5%)		3/7 (42.9%)		0/4 (0%)		2/4 (50%)
Vomiting	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		2/4 (50%)
Abdominal distention	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Dyspepsia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Gastrooesophageal reflux disease	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		1/4 (25%)		0/4 (0%)
Dry mouth	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Reflux oesophagitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
General disorders
Chest discomfort	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Early satiety	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Fatigue	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		1/8 (12.5%)		2/7 (28.6%)		0/4 (0%)		1/4 (25%)
Oedema peripheral	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		4/7 (57.1%)		0/4 (0%)		0/4 (0%)
Pyrexia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Thirst	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		1/4 (25%)		1/4 (25%)
Immune system disorders
Graft versus host disease	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Hypogammaglobulinaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Infections and infestations
Nasopharyngitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		1/4 (25%)		0/4 (0%)
Upper respiratory tract infection	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		1/4 (25%)		0/4 (0%)
Urinary tract infection	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Cystitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Oral fungal infection	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Sinusitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Cellulitis	0/1 (0%)		0/1 (0%)		1/1 (100%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Gastroenteritis viral	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Post procedural haemorrhage	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		1/4 (25%)		0/4 (0%)
Procedural pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Hand fracture	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Investigations
Blood amylase increased	1/1 (100%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Lipase increased	1/1 (100%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Blood creatinine increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Gamma-glutamyltransferase increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Haematocrit decreased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Blood lactate dehydrogenase increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Blood creatine phosphokinase increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Metabolism and nutrition disorders
Anorexia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Fluid overload	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Hypercholesterolaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Hyperkalaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Lactose intolerance	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Hyperlipidemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		1/4 (25%)		0/4 (0%)
Arthralgia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Muscle tightness	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Muscular weakness	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Musculoskeletal discomfort	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Pain in jaw	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Osteopenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		2/2 (100%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		2/4 (50%)
Osteoporosis	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Nervous system disorders
Dizziness	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		2/7 (28.6%)		0/4 (0%)		0/4 (0%)
Headache	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		2/8 (25%)		2/7 (28.6%)		0/4 (0%)		2/4 (50%)
Tremor	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Psychiatric disorders
Insomnia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Renal and urinary disorders
Dysuria	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Renal failure	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Urinary retention	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Dyspnoea	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		3/7 (42.9%)		0/4 (0%)		0/4 (0%)
Dyspnoea exertional	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Nasal congestion	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Pharyngolaryngeal pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Rales	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Sinus congestion	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		2/7 (28.6%)		0/4 (0%)		0/4 (0%)
Throat irritation	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Rhinorrhoea	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Oxygen saturation decreased	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/2 (50%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Epistaxis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Skin and subcutaneous tissue disorders
Pruritus	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		1/4 (25%)		0/4 (0%)
Rash	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Rash papular	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		1/4 (25%)
Ecchymosis	0/1 (0%)		0/1 (0%)		1/1 (100%)		0/2 (0%)		0/8 (0%)		0/7 (0%)		0/4 (0%)		0/4 (0%)
Erythema	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/8 (0%)		1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Vascular disorders
Hypertension	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		1/8 (12.5%)		0/7 (0%)		0/4 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Within 12 months after the end of the Study at all sites, if no publication of the overall multi-center results has been made, institutions are entitled to publish their locally obtained results, provided the Sponsor is given opportunity to review and comment.