Phase II Study of Intraperitoneal NanoPac® in Patients With Ovarian Cancer

• Sponsor: NanOlogy, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03029585
• Collaborator: US Biotest, Inc. (Industry)
• Enrollment: 10
• Locations: 7
• Arms: 5
• Actual Duration (Months): 30.5
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate NanoPac® administered intraperitoneally (IP) immediately post-cytoreductive surgery, followed by standard of care (SOC) intravenous (IV) chemotherapy, in women with ovarian cancer. The study will compare IP NanoPac® (plus IV chemotherapy) with SOC IV chemotherapy alone.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Carcinoma	Drug: NanoPac® 100 mg/m2; Drug: NanoPac® 200 mg/m2; Drug: NanoPac® 300 mg/m2; Drug: NanoPac® 400 mg/m2; Drug: Standard of Care Intravenous Chemotherapy	Phase 2

Detailed Description

Research has shown that the administration of chemotherapy directly into the peritoneal cavity (intraperitoneal [IP] chemotherapy) may provide a significant survival benefit to women with ovarian cancer when combined with cytoreductive surgery and IV chemotherapy.

This study will include a dose-finding phase and an efficacy phase to evaluate IP NanoPac® administered immediately post-cytoreductive surgery in women with ovarian cancer. In the dose-finding phase, subjects will be enrolled in dose-escalated cohorts of three subjects and receive IP NanoPac® at 100, 200, 300, or 400 mg/m2 plus standard of care (SOC) IV chemotherapy. Subjects will be followed for disease status for 12 months. The two best doses from the dose-finding phase will be determined. In the efficacy phase, subjects will be randomized 1:1:1 to one of the two best doses plus SOC IV chemotherapy or SOC alone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Four Dose Levels of Intraperitoneal NanoPac® Plus IV Carboplatin and Paclitaxel in Patients With Epithelial Ovarian Cancer Undergoing Cytoreductive Surgery
• Actual Study Start Date: Apr 19, 2017
• Actual Primary Completion Date: Nov 4, 2019
• Actual Study Completion Date: Nov 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NanoPac® 100 mg/m2 Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.	Drug: NanoPac® 100 mg/m2; Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment; Drug: Standard of Care Intravenous Chemotherapy; Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Experimental: NanoPac® 200 mg/m2 Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.	Drug: NanoPac® 200 mg/m2; Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment; Drug: Standard of Care Intravenous Chemotherapy; Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Experimental: NanoPac® 300 mg/m2 Intraperitoneal NanoPac® 300 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.	Drug: NanoPac® 300 mg/m2; Single intraperitoneal injection of 300 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment; Drug: Standard of Care Intravenous Chemotherapy; Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Experimental: NanoPac® 400 mg/m2 Intraperitoneal NanoPac® 400 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.	Drug: NanoPac® 400 mg/m2; Single intraperitoneal injection of 400 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment; Drug: Standard of Care Intravenous Chemotherapy; Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Active Comparator: Standard of Care Intravenous Chemotherapy Standard of care intravenous chemotherapy (with platinum and taxane agents) administered per institutional standards.	Drug: Standard of Care Intravenous Chemotherapy; Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment

Outcome Measures

Primary Outcome Measures

1. Treatment-emergent Adverse Events [12 months]

   Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus).

Secondary Outcome Measures

1. Maximum Plasma Concentration of Paclitaxel (Cmax) [12 months]

   Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively.

2. Progression Free Survival (PFS) at 12 Months [12 months post-treatment]

   Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Epithelial ovarian cancer which is contained within the abdomen, but may include pleural effusion if that is the limit of non-peritoneal cavity disease. If subject has recurrent epithelial ovarian cancer, the disease must be platinum sensitive (recurrence >6 months from prior chemotherapy regimen that included a platinum agent and cytoreductive surgery)

• Subject appropriate for cytoreductive surgery and treatment with IV platinum and paclitaxel

• Minimal or non-symptomatic ascites

• ≥18 years old

• Signed informed consent

Exclusion Criteria:

• Epithelial ovarian cancer outside of the peritoneal cavity, with the exception of pleural effusions

• Anticipated use of concomitant chemotherapy (other than the protocol-specified agents), immunotherapy, or radiation therapy

• Treatment with a prior investigational agent within 30 days of planned instillation of NanoPac®, with the exception of subjects participating in poly (ADP-ribose) polymerase (PARP) inhibitor trials. These subjects must discontinue the investigational agent prior to surgery

• Known sensitivity to any of the study medication components or the chemotherapy regimen

• History of prior malignancy other than ovarian that has not been in remission for >5 years, with the exception of basal cell or squamous cell carcinoma or cervical carcinoma in situ on biopsy

• Ileostomy or hepatic resection during current cytoreductive surgery

• Women of childbearing potential not practicing adequate forms of birth control

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637
2	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
3	University of Minnesota	Minneapolis	Minnesota	United States	55455
4	SUNY Downstate	Brooklyn	New York	United States	11203
5	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania	United States	15213
6	Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
7	University of Texas Southwestern	Dallas	Texas	United States	75390

Sponsors and Collaborators

• NanOlogy, LLC
• US Biotest, Inc.

Investigators

• Principal Investigator: Joan Walker, MD, University of Oklahoma
• Study Chair: Gere diZerega, MD, US Biotest, Inc./NanOlogy, LLC

Study Documents (Full-Text)

• Study Protocol - Apr 19, 2019
• Statistical Analysis Plan - Jan 29, 2020

More Information

Publications

None provided.

• Responsible Party: NanOlogy, LLC
• ClinicalTrials.gov Identifier: NCT03029585
• Other Study ID Numbers: NANOPAC-2016-01
• First Posted: Jan 24, 2017
• Last Update Posted: Apr 27, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by NanOlogy, LLC: ovarian carcinoma; ovarian cancer; ovarian neoplasms; ovarian diseases
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Study Results

Participant Flow

Arm/Group Title	NanoPac® 100 mg/m2	NanoPac® 200 mg/m2
Arm/Group Description	Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment	Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Period Title: Overall Study
STARTED	7	3
COMPLETED	5	2
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	NanoPac® 100 mg/m2	NanoPac® 200 mg/m2	Total
Arm/Group Description	Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment	Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment	Total of all reporting groups
Overall Participants	7	3	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68	62	67
Sex: Female, Male (Count of Participants)
Female	7 100%	3 100%	10 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 14.3%	0 0%	1 10%
White	6 85.7%	3 100%	9 90%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Disease Status (Count of Participants)
Primary	4 57.1%	2 66.7%	6 60%
Recurrent	3 42.9%	1 33.3%	4 40%
ECOG Status (Count of Participants)
ECOG 0	5 71.4%	2 66.7%	7 70%
ECOG 1	2 28.6%	1 33.3%	3 30%
Status of Ovarian Cancer at Screening (Count of Participants)
IIIA2	0 0%	1 33.3%	1 10%
IIIB	2 28.6%	0 0%	2 20%
IIIC	4 57.1%	1 33.3%	5 50%
IVB	1 14.3%	1 33.3%	2 20%

Outcome Measures

1. Primary Outcome

Title	Treatment-emergent Adverse Events
Description	Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NanoPac® 100 mg/m2	NanoPac® 200 mg/m2
Arm/Group Description	Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment	Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Measure Participants	7	3
Number [Treatment Emergent Adverse Events]	80	28

2. Secondary Outcome

Title	Maximum Plasma Concentration of Paclitaxel (Cmax)
Description	Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NanoPac® 100 mg/m2	NanoPac® 200 mg/m2
Arm/Group Description	Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment	Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Measure Participants	7	3
Mean (Standard Deviation) [ng/mL]	12.56 (10.98)	26.50 (13.56)

3. Secondary Outcome

Title	Progression Free Survival (PFS) at 12 Months
Description	Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites.
Time Frame	12 months post-treatment

Outcome Measure Data

Analysis Population Description

Of the 10 subjects enrolled, four subjects were not evaluable for PFS at 12 months post-NanoPac instillation. For one subject, no imaging was performed over the course of the study; one subject was deceased due to leptomeningeal carcinomatosis; one subject was deceased due to a respiratory arrest; and one subject withdrew consent from the study. Both deaths were considered not related to study medication by the Investigator and the Medical Monitor.

Arm/Group Title	NanoPac® 100 mg/m2	NanoPac® 200 mg/m2
Arm/Group Description	Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment	Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Measure Participants	4	2
PFS at 12 months	4 57.1%	0 0%
Disease Progression	0 0%	2 66.7%

Adverse Events

Time Frame	AEs were collected at all study visits from the time of dosing until end of study, for a planned 30-month collection period for each subject.
Arm/Group Title	NanoPac® 100 mg/m2		NanoPac® 200 mg/m2
Arm/Group Description	Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment		Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
All Cause Mortality
	NanoPac® 100 mg/m2		NanoPac® 200 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		1/3 (33.3%)
Serious Adverse Events
	NanoPac® 100 mg/m2		NanoPac® 200 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)		3/3 (100%)
Infections and infestations
Pyelonephritis	1/7 (14.3%)	1	0/3 (0%)	0
Cellulitis	0/7 (0%)	0	1/3 (33.3%)	1
Pelvic abscess	1/7 (14.3%)	1	0/3 (0%)	0
Cystitis	1/7 (14.3%)	1	0/3 (0%)	0
Injury, poisoning and procedural complications
Wound dehiscence	1/7 (14.3%)	1	1/3 (33.3%)	1
Wound necrosis	0/7 (0%)	0	1/3 (33.3%)	1
Metabolism and nutrition disorders
Hyperglycaemia	1/7 (14.3%)	1	0/3 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges	0/7 (0%)	0	1/3 (33.3%)	1
Psychiatric disorders
Major depression	0/7 (0%)	0	1/3 (33.3%)	1
Reproductive system and breast disorders
Pelvic fluid collection	0/7 (0%)	0	1/3 (33.3%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory arrest	1/7 (14.3%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	NanoPac® 100 mg/m2		NanoPac® 200 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	1/7 (14.3%)	5	1/3 (33.3%)	1
Leukocytosis	2/7 (28.6%)	3	1/3 (33.3%)	1
Thrombocytosis	1/7 (14.3%)	1	0/3 (0%)	0
Cardiac disorders
Arrhythmia	1/7 (14.3%)	1	0/3 (0%)	0
Palpitations	1/7 (14.3%)	1	0/3 (0%)	0
Tachycardia	1/7 (14.3%)	1	0/3 (0%)	0
Gastrointestinal disorders
Abdominal distension	2/7 (28.6%)	2	0/3 (0%)	0
Abdominal pain	0/7 (0%)	0	1/3 (33.3%)	1
Ascites	1/7 (14.3%)	1	0/3 (0%)	0
Constipation	2/7 (28.6%)	2	1/3 (33.3%)	1
Diarrhoea	1/7 (14.3%)	1	1/3 (33.3%)	1
Gastrooesophageal Reflux	1/7 (14.3%)	1	0/3 (0%)	0
Ileus	0/7 (0%)	0	1/3 (33.3%)	1
Ileus paralytic	1/7 (14.3%)	1	0/3 (0%)	0
Nausea	3/7 (42.9%)	5	3/3 (100%)	3
Vomiting	2/7 (28.6%)	3	2/3 (66.7%)	2
General disorders
Administration site extravasation	1/7 (14.3%)	1	0/3 (0%)	0
Fatigue	3/7 (42.9%)	5	1/3 (33.3%)	1
Pain	0/7 (0%)	0	1/3 (33.3%)	1
Pyrexia	1/7 (14.3%)	1	1/3 (33.3%)	1
Infections and infestations
Pneumonia	0/7 (0%)	0	1/3 (33.3%)	1
Pyelonephritis	1/7 (14.3%)	1	0/3 (0%)	0
Urinary tract infection	2/7 (28.6%)	2	1/3 (33.3%)	1
Injury, poisoning and procedural complications
Incision site pain	1/7 (14.3%)	3	0/3 (0%)	0
Procedural pain	4/7 (57.1%)	4	2/3 (66.7%)	2
Investigations
Blood albumin decreased	1/7 (14.3%)	1	0/3 (0%)	0
Blood chloride decreased	1/7 (14.3%)	1	0/3 (0%)	0
Blood urea decreased	1/7 (14.3%)	1	0/3 (0%)	0
Glomerular filtration rate decreased	1/7 (14.3%)	1	0/3 (0%)	0
Haematocrit decreased	1/7 (14.3%)	1	0/3 (0%)	0
Heart rate irregular	1/7 (14.3%)	1	0/3 (0%)	0
Lymphocyte count	0/7 (0%)	0	1/3 (33.3%)	1
Platelet count decreased	1/7 (14.3%)	1	0/3 (0%)	0
Protein total decreased	1/7 (14.3%)	1	1/3 (33.3%)	1
White blood cell count increased	2/7 (28.6%)	2	0/3 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/7 (0%)	0	1/3 (33.3%)	1
Hyperglycaemia	2/7 (28.6%)	4	0/3 (0%)	0
Hypermagnesaemia	1/7 (14.3%)	1	0/3 (0%)	0
Hypoalbuminaemia	0/7 (0%)	0	1/3 (33.3%)	1
Hypocalcaemia	1/7 (14.3%)	2	1/3 (33.3%)	2
Hypokalacaemia	2/7 (28.6%)	2	1/3 (33.3%)	1
Hyponatraemia	1/7 (14.3%)	1	0/3 (0%)	0
Hypophosphataemia	2/7 (28.6%)	3	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/7 (14.3%)	1	0/3 (0%)	0
Flank pain	1/7 (14.3%)	1	0/3 (0%)	0
Muscular weakness	1/7 (14.3%)	1	0/3 (0%)	0
Pain in extremity	1/7 (14.3%)	1	0/3 (0%)	0
Nervous system disorders
Dizziness	1/7 (14.3%)	1	0/3 (0%)	0
Hypoaesthesia	1/7 (14.3%)	1	0/3 (0%)	0
Renal and urinary disorders
Haematuria	1/7 (14.3%)	1	0/3 (0%)	0
Hydronephrosis	0/7 (0%)	0	1/3 (33.3%)	1
Urinary incontinence	1/7 (14.3%)	1	0/3 (0%)	0
Reproductive system and breast disorders
Pelvic fluid collection	0/7 (0%)	0	1/3 (33.3%)	1
Pelvic pain	0/7 (0%)	0	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/7 (14.3%)	1	0/3 (0%)	0
Nasal congestion	1/7 (14.3%)	1	0/3 (0%)	0
Oropharyngeal pain	1/7 (14.3%)	1	0/3 (0%)	0
Vascular disorders
Hypotension	1/7 (14.3%)	1	0/3 (0%)	0

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.