Study Evaluating Rapamune® Maintenance Regimen

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00478608
• Collaborator: (none)
• Enrollment: 79
• Locations: 9
• Duration (Months): 20.1
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Primary : To evaluate the efficacy of sirolimus assessed by the incidence of biopsy-confirmed acute rejection episode at 6 months after transplantation in Korean renal transplantation recipients.

Secondary :

1. To evaluate the safety of sirolimus over 12 months after transplantation in Korean renal transplantation recipients.

2. To evaluate graft function, patient survival and graft survival at 6 and 12 months after transplantation, and to investigate the incidence of biopsy-confirmed acute rejection episode at 12 months after transplantation.

Condition or Disease	Intervention/Treatment	Phase
Renal Transplant	Drug: Sirolimus (Rapamune®)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Clinical Study to Evaluate the Efficacy and Safety of Cyclosporine (CsA) and Sirolimus (SRL) Induction Followed by Cyclosporine Withdrawal in Korean Renal Allograft Recipients
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Outcome Measures

Primary Outcome Measures

1. Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 6 After Transplantation. [6 months after transplantation]

   The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions).

Secondary Outcome Measures

1. Glomerular Filtration Rate (GFR) (Nankivell Method) [6 and 12 months]

   GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. For this study, GFR was calculated using the Nankivell formula. A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poorer kidney function. A GFR <15 is consistent with kidney failure.

2. Serum Creatinine [Baseline, 6 and 12 months]

   Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass.

3. Patient and Graft Survival [12 months]

   Patient survival defined as patients living with or without a functioning graft. Graft survival defined as those patients who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.

4. Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 12 After Transplantation [12 months after transplantation]

   The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age greater than or equal to 13 years of age.

2. End-stage renal disease in patients scheduled to receive a primary renal allograft from a cadaveric donor, a living-unrelated donor, or from a living-related (excluding 0 antigen mismatch) donor. A mismatch donor is defined as a donor human leukocyte antigen (HLA) antigen not shared by the patient.

3. Patients with a panel of reactive antibody (%PRA) less than or equal to 50%

Exclusion Criteria:

1. Evidence of active systemic or localized major infection at the time of initial sirolimus administration.

2. Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during pre-study screening.

3. Chronic anti-arrhythmic therapy for ventricular arrhythmia or other cardiac abnormality contraindicating general anesthesia or surgery.

4. History of malignancy within 5 years before enrollment into the study (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin).

5. Current treatment with partial opioid agonists (eg, buprenorphine) or combination agonists/antagonists.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Deagu		Korea, Republic of	700-712
2		Deagu		Korea, Republic of	700-721
3		Pusan		Korea, Republic of	614-735
4		Seoul		Korea, Republic of	110-744
5		Seoul		Korea, Republic of	120-752
6		Seoul		Korea, Republic of	135-710
7		Seoul		Korea, Republic of	137-701
8		Seoul		Korea, Republic of	138-736
9		Suwon		Korea, Republic of	443-721

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Medical Monitor, Wyeth is now a wholly owned subsidiary of Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00478608
• Other Study ID Numbers: 0468E-102362
• First Posted: May 25, 2007
• Last Update Posted: Apr 28, 2010
• Last Verified: Apr 1, 2010

• Additional relevant MeSH terms: Sirolimus

Study Results

Participant Flow

Recruitment Details	Patients were recruited in Korea from March 2007 to November 2007.
Pre-assignment Detail	Patients were screened up to 7 days.

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
Period Title: Overall Study
STARTED	79
COMPLETED	59
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
Overall Participants	79
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.16 (12.69)
Sex: Female, Male (Count of Participants)
Female	47 59.5%
Male	32 40.5%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 6 After Transplantation.
Description	The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions).
Time Frame	6 months after transplantation

Outcome Measure Data

Analysis Population Description

Patients who received at least one dosing of SRL after transplantation.

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
Measure Participants	79
Number [patients]	12

2. Secondary Outcome

Title	Glomerular Filtration Rate (GFR) (Nankivell Method)
Description	GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. For this study, GFR was calculated using the Nankivell formula. A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poorer kidney function. A GFR <15 is consistent with kidney failure.
Time Frame	6 and 12 months

Outcome Measure Data

Analysis Population Description

Patients who received at least one dose of SRL after transplantation. Observed values

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
Measure Participants	79
6 months	67.36 (15.25)
12 months	71.92 (18.82)

3. Secondary Outcome

Title	Serum Creatinine
Description	Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass.
Time Frame	Baseline, 6 and 12 months

Outcome Measure Data

Analysis Population Description

Patients who received at least one dose of SRL after transplantation. Observed values

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
Measure Participants	79
Baseline	9.42 (3.64)
6 months	1.30 (0.36)
12 months	1.25 (0.43)

4. Secondary Outcome

Title	Patient and Graft Survival
Description	Patient survival defined as patients living with or without a functioning graft. Graft survival defined as those patients who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Patients who received at least one dosing of SRL after transplantation.

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
Measure Participants	79
Patient survival 6 months	77
Patient survival 12 months	76
Graft survival 6 months	77
Graft survival 12 months	76

5. Secondary Outcome

Title	Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 12 After Transplantation
Description	The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions).
Time Frame	12 months after transplantation

Outcome Measure Data

Analysis Population Description

Patients who received at least one dosing of SRL after transplantation.

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
Measure Participants	79
Number [patients]	15

Adverse Events

Arm/Group Title	Sirolimus (SRL)
Arm/Group Description	Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn. On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml. CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks. Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited.
All Cause Mortality
	Sirolimus (SRL)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sirolimus (SRL)
	Affected / at Risk (%)	# Events
Total	39/79 (49.4%)
Blood and lymphatic system disorders
Haemolytic uraemic syndrome	1/79 (1.3%)
Thrombocytopenia	1/79 (1.3%)
Cardiac disorders
Myocardial infarction	1/79 (1.3%)
Cardiac failure congestive	1/79 (1.3%)
Myocarditis	1/79 (1.3%)
Gastrointestinal disorders
Diarrhoea	3/79 (3.8%)
Abdominal pain	1/79 (1.3%)
Abdominal hernia	1/79 (1.3%)
Inguinal hernia	1/79 (1.3%)
Haematochezia	1/79 (1.3%)
Faecaloma	1/79 (1.3%)
General disorders
Pyrexia	2/79 (2.5%)
Oedema peripheral	1/79 (1.3%)
Oedema	1/79 (1.3%)
Asthenia	1/79 (1.3%)
Death	3/79 (3.8%)
Infections and infestations
Herpes zoster	6/79 (7.6%)
Pneumonia	5/79 (6.3%)
Gastroenteritis	2/79 (2.5%)
Urinary tract infection	2/79 (2.5%)
Varicella	1/79 (1.3%)
Parotitis	1/79 (1.3%)
Pulmonary tuberculosis	1/79 (1.3%)
Enterocolitis infectious	1/79 (1.3%)
Fungal infection	1/79 (1.3%)
Cellulitis	1/79 (1.3%)
Injury, poisoning and procedural complications
Seroma	1/79 (1.3%)
Investigations
Blood creatinine increased	10/79 (12.7%)
Aspartate aminotransferase increased	1/79 (1.3%)
Blood glucose increased	1/79 (1.3%)
Alanine aminotransferase increased	1/79 (1.3%)
Metabolism and nutrition disorders
Hyperglycaemia	2/79 (2.5%)
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/79 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma	1/79 (1.3%)
Renal and urinary disorders
Urinary incontinence	1/79 (1.3%)
Renal mass	1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory arrest	1/79 (1.3%)
Pneumothorax	1/79 (1.3%)
Asphyxia	1/79 (1.3%)
Vascular disorders
Lymphocele	6/79 (7.6%)
Other (Not Including Serious) Adverse Events
	Sirolimus (SRL)
	Affected / at Risk (%)	# Events
Total	79/79 (100%)
Blood and lymphatic system disorders
Anaemia	19/79 (24.1%)
Leukopenia	4/79 (5.1%)
Neutropenia	1/79 (1.3%)
Thrombocytopenia	1/79 (1.3%)
Leukocytosis	1/79 (1.3%)
Cardiac disorders
Arrhythmia	2/79 (2.5%)
Palpitations	1/79 (1.3%)
Myocardial infarction	1/79 (1.3%)
Angina pectoris	1/79 (1.3%)
Ear and labyrinth disorders
Hypoacusis	1/79 (1.3%)
Ear pain	1/79 (1.3%)
Endocrine disorders
Hyperthyroidism	2/79 (2.5%)
Cushingoid	2/79 (2.5%)
Eye disorders
Visual disturbance	2/79 (2.5%)
Vision blurred	1/79 (1.3%)
Xerophthalmia	1/79 (1.3%)
Ocular hyperaemia	1/79 (1.3%)
Conjunctivitis	1/79 (1.3%)
Dry eye	1/79 (1.3%)
Eyelid oedema	1/79 (1.3%)
Conjunctival oedema	1/79 (1.3%)
Gastrointestinal disorders
Constipation	31/79 (39.2%)
Diarrhoea	21/79 (26.6%)
Nausea	16/79 (20.3%)
Mouth ulceration	14/79 (17.7%)
Vomiting	13/79 (16.5%)
Abdominal pain	12/79 (15.2%)
Dyspepsia	8/79 (10.1%)
Abdominal pain upper	7/79 (8.9%)
Abdominal discomfort	5/79 (6.3%)
Stomatitis	5/79 (6.3%)
Abdominal distension	4/79 (5.1%)
Gingival hyperplasia	2/79 (2.5%)
Epigastric discomfort	1/79 (1.3%)
Haematemesis	1/79 (1.3%)
Oral disorder	1/79 (1.3%)
Gastrointestinal disorder	1/79 (1.3%)
Oral discomfort	1/79 (1.3%)
Faecal incontinence	1/79 (1.3%)
Dental caries	1/79 (1.3%)
Anorectal disorder	1/79 (1.3%)
Abdominal pain lower	1/79 (1.3%)
General disorders
Pyrexia	8/79 (10.1%)
Chest discomfort	7/79 (8.9%)
Oedema peripheral	6/79 (7.6%)
Generalised oedema	5/79 (6.3%)
Oedema	5/79 (6.3%)
Pitting oedema	2/79 (2.5%)
Face oedema	2/79 (2.5%)
Chest pain	2/79 (2.5%)
Catheter site pain	1/79 (1.3%)
Mass	1/79 (1.3%)
Influenza like illness	1/79 (1.3%)
Swelling	1/79 (1.3%)
Sense of oppression	1/79 (1.3%)
Xerosis	1/79 (1.3%)
Hepatobiliary disorders
Hepatitis	2/79 (2.5%)
Hepatotoxicity	1/79 (1.3%)
Hyperbilirubinaemia	1/79 (1.3%)
Infections and infestations
Upper respiratory tract infection	26/79 (32.9%)
Nasopharyngitis	12/79 (15.2%)
Urinary tract infection	6/79 (7.6%)
Herpes zoster	6/79 (7.6%)
Herpes simplex	4/79 (5.1%)
Rhinitis	2/79 (2.5%)
Oral candidiasis	2/79 (2.5%)
Tinea versicolour	2/79 (2.5%)
Tinea pedis	2/79 (2.5%)
Varicella	1/79 (1.3%)
Vaginal infection	1/79 (1.3%)
Tinea cruris	1/79 (1.3%)
Folliculitis	1/79 (1.3%)
Bacteraemia	1/79 (1.3%)
BK virus infection	1/79 (1.3%)
Infection	1/79 (1.3%)
Skin infection	1/79 (1.3%)
Rash pustular	1/79 (1.3%)
Gingival infection	1/79 (1.3%)
Fungal infection	1/79 (1.3%)
Gastroenteritis	1/79 (1.3%)
Orchitis	1/79 (1.3%)
Injury, poisoning and procedural complications
Procedural pain	24/79 (30.4%)
Post procedural complication	2/79 (2.5%)
Postoperative wound complication	1/79 (1.3%)
Post procedural haemorrhage	1/79 (1.3%)
Femur fracture	1/79 (1.3%)
Investigations
Blood cholesterol increased	29/79 (36.7%)
Alanine aminotransferase increased	17/79 (21.5%)
Aspartate aminotransferase increased	12/79 (15.2%)
Urine output decreased	11/79 (13.9%)
Blood lactate dehydrogenase increased	10/79 (12.7%)
Blood creatinine increased	9/79 (11.4%)
Hepatic enzyme increased	9/79 (11.4%)
Blood triglycerides increased	8/79 (10.1%)
Blood glucose increased	8/79 (10.1%)
Weight increased	5/79 (6.3%)
Blood pressure increased	4/79 (5.1%)
Blood phosphorus decreased	3/79 (3.8%)
Haemoglobin decreased	3/79 (3.8%)
Blood albumin decreased	3/79 (3.8%)
Blood potassium increased	2/79 (2.5%)
Blood uric acid increased	2/79 (2.5%)
Body temperature increased	1/79 (1.3%)
Platelet count decreased	1/79 (1.3%)
Blood potassium decreased	1/79 (1.3%)
Gamma-glutamyltransferase increased	1/79 (1.3%)
Blood calcium decreased	1/79 (1.3%)
Blood alkaline phosphatase increased	1/79 (1.3%)
Blood calcium increased	1/79 (1.3%)
White blood cells urine positive	1/79 (1.3%)
White blood cell count decreased	1/79 (1.3%)
Metabolism and nutrition disorders
Hypercholesterolaemia	19/79 (24.1%)
Hyperlipidaemia	12/79 (15.2%)
Hyperkalaemia	8/79 (10.1%)
Hypokalaemia	6/79 (7.6%)
Hypoalbuminaemia	5/79 (6.3%)
Hyperglycaemia	5/79 (6.3%)
Diabetes mellitus	4/79 (5.1%)
Hypophosphataemia	2/79 (2.5%)
Hyponatraemia	2/79 (2.5%)
Hypoglycaemia	2/79 (2.5%)
Hypocalcaemia	1/79 (1.3%)
Electrolyte imbalance	1/79 (1.3%)
Anorexia	1/79 (1.3%)
Hyperamylasaemia	1/79 (1.3%)
Musculoskeletal and connective tissue disorders
Back pain	11/79 (13.9%)
Arthralgia	6/79 (7.6%)
Musculoskeletal pain	3/79 (3.8%)
Pain in extremity	3/79 (3.8%)
Myalgia	2/79 (2.5%)
Osteoporosis	2/79 (2.5%)
Neck pain	1/79 (1.3%)
Musculoskeletal discomfort	1/79 (1.3%)
Muscle spasms	1/79 (1.3%)
Coccydynia	1/79 (1.3%)
Arthritis	1/79 (1.3%)
Nervous system disorders
Headache	15/79 (19%)
Convulsion	3/79 (3.8%)
Dizziness	2/79 (2.5%)
Paraesthesia	2/79 (2.5%)
Tremor	2/79 (2.5%)
Neuropathy peripheral	1/79 (1.3%)
Neuralgia	1/79 (1.3%)
Migraine	1/79 (1.3%)
Somnolence	1/79 (1.3%)
Hypoaesthesia	1/79 (1.3%)
Dysarthria	1/79 (1.3%)
Psychiatric disorders
Insomnia	12/79 (15.2%)
Sleep disorder	2/79 (2.5%)
Renal and urinary disorders
Haematuria	7/79 (8.9%)
Proteinuria	3/79 (3.8%)
Azotaemia	2/79 (2.5%)
Albuminuria	1/79 (1.3%)
Pollakiuria	1/79 (1.3%)
Renal tubular necrosis	1/79 (1.3%)
Reproductive system and breast disorders
Amenorrhoea	4/79 (5.1%)
Ovarian cyst	2/79 (2.5%)
Erectile dysfunction	2/79 (2.5%)
Benign prostatic hyperplasia	1/79 (1.3%)
Vaginal haemorrhage	1/79 (1.3%)
Genital haemorrhage	1/79 (1.3%)
Dysmenorrhoea	1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Cough	8/79 (10.1%)
Rhinorrhoea	7/79 (8.9%)
Dyspnoea	6/79 (7.6%)
Productive cough	3/79 (3.8%)
Pharyngolaryngeal pain	2/79 (2.5%)
Rhinitis allergic	1/79 (1.3%)
Hiccups	1/79 (1.3%)
Skin and subcutaneous tissue disorders
Acne	18/79 (22.8%)
Pruritus	10/79 (12.7%)
Rash	7/79 (8.9%)
Hirsutism	2/79 (2.5%)
Rash papular	1/79 (1.3%)
Ecchymosis	1/79 (1.3%)
Periorbital oedema	1/79 (1.3%)
Neurodermatitis	1/79 (1.3%)
Skin disorder	1/79 (1.3%)
Dry skin	1/79 (1.3%)
Dermal cyst	1/79 (1.3%)
Dermatitis acneiform	1/79 (1.3%)
Rash macular	1/79 (1.3%)
Blister	1/79 (1.3%)
Alopecia	1/79 (1.3%)
Toxic skin eruption	1/79 (1.3%)
Swelling face	1/79 (1.3%)
Vascular disorders
Hypertension	6/79 (7.6%)
Lymphocele	1/79 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.