DRESS: Delafloxacin IV and OS Administration Compared to Best Available Therapy in Patients With Surgical Site Infections

• Sponsor: Menarini Group (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04042077
• Collaborator: (none)
• Enrollment: 268
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.1
• Patients Per Site Per Month: 20.4

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of delafloxacin administered as IV and oral formulation in comparison with Best Available Therapy (BAT) in patients with superficial or deep incisional surgical site infection following a cardiothoracic/related leg or abdominal surgery.

Condition or Disease	Intervention/Treatment	Phase
Surgical Site Infection	Drug: Delafloxacin; Drug: Vancomycin; Drug: Linezolid; Drug: Piperacillin/Tazobactam; Drug: Tigecycline	Phase 3

Detailed Description

This is a randomized, observer-blinded, active-controlled, parallel-group, multicenter, phase IIIb study for the treatment of incisional, superficial or deep, surgical site infection after cardiothoracic /related leg or abdominal surgery (i.e patients who are at risk of microbiologically resistant infections). IV to be switched to oral delafloxacin will be compared to treatments that represent the best available therapy (BAT) for either cardiothoracic/related leg or abdominal surgical site infection (SSI).

Approximately 600 male and female eligible patients will be randomly assigned in a 1:1 ratio to receive delafloxacin or BAT. For patients who are randomised to BAT, the investigator will choose one out of two treatments available (two available for the cardiothoracic/related leg and two available for abdominal SSI) as most appropriate for patient characteristics and local epidemiological pattern.

Duration of study depends on treatment duration (range: minimum 5 to maximum 14 days, as per Investigator's judgment) followed by visits up to 30 days after end of treatment.

Patients will be hospitalized from Screening (within 30 days from surgery) and will remain hospitalized until considered improved or cure as per Investigator's judgment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 268 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The study will compare delafloxacin against best available therapy selected by the investigator for the cardiothoracic/leg related or abdominal site infectionThe study will compare delafloxacin against best available therapy selected by the investigator for the cardiothoracic/leg related or abdominal site infection
• Masking: Single (Outcomes Assessor)
• Masking Description: Only the blinded observer will be unaware of the treatment assigned to patient.
• Primary Purpose: Treatment
• Official Title: A Randomized, Observer-blinded, Active-controlled, Phase Illb Study to Compare IV / Oral Delafloxacin Fixed-dose Monotherapy With Best Available Treatments in a Microbiologically Enriched Population With Surgical Site Infections
• Actual Study Start Date: Sep 25, 2019
• Actual Primary Completion Date: Oct 7, 2020
• Actual Study Completion Date: Oct 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Delafloxacin Delafloxacin IV, with the option to switch to delafloxacin oral	Drug: Delafloxacin; Powder for solution for infusion 300 mg or tablet 450 mg, BID, for 5 to 14 days
Active Comparator: Best Available Therapy Cardiothoracic / related leg SSI Vancomycin IV Linezolid IV, with the option to switch to linezolid oral. In case of suspicion of Gram-negative, additional therapy shall be added as per investigator's choice Abdominal SSI Piperacillin/Tazobactam IV, OR Tigecycline IV In case of suspicion of MRSA, if the pre-selected treatment is Piperacillin/Tazobactam, additional therapy shall be added as per investigator's choice.	Drug: Vancomycin; Powder for solution for infusion 15mg/kg, BID, for 5 to 14 days; Drug: Linezolid; Solution for infusion or tablet, 600 mg BID, for 5 to 14 days; Drug: Piperacillin/Tazobactam; Powder for solution for infusion 4/0.5 g, TID, for 5 to 14 days; Drug: Tigecycline; Powder for solution for infusion 50 mg, TID, for 5 to 14 days

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Success at Test Of Cure Visit [7-14 days after last dose]

   Clinical Success defined as the clinical response of "Cure" or "improved". Below the definitions: Cure: The complete resolution of all baseline signs and symptoms of SSI Improved: two or more signs and/or symptoms (but not all) were considered resolved thus the patient had improved to an extent that no additional antibiotic treatment was necessary.

Secondary Outcome Measures

1. Hospital Infection Related Length of Stay (IRLOS) [up to 14 days]

   Length of Stay since beginning of therapy till patient stabilization and considered suitable for hospital discharge

2. Hospital Length of Stay (LOS) [up to 45 days (Late Follow Up visit)]

   Length of Stay since Screening till actual hospital discharge

3. Number of Participants Eligible to Switch to Oral Formulation According to Blinded Observer's Assessment [up to 14 days]

   Blinded assessment based on patient stabilization and ability to tolerate OS diet. In particular, the following details had to be met: Systolic blood pressure normal/not clinically significant abnormal No infection related tachycardia Afebrile status; body temperature <38°C for at least 24 hours* WBC count normalized/not clinically significant abnormal Patient able to tolerate PO diet/to take PO treatment and no GI absorption problem The measure counts only the participants eligible to switch, without taking into account the actually switched. Indeed, only linezolid in the BAT has an equivalent oral formulation suitable for the switch.

4. Microbiological Response [up to 14 days (End Of Treatment visit) and 7-14 days after last dose (Test Of Cure visit)]

   Documented or presumed eradication or persistence

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female patients aged more than 18 years.

• Patients with a history of cardiothoracic / related leg or abdominal surgery, occurred within 30 days and no implant is left in place, and a diagnosis of superficial or deep SSI according to the CDC definition.

• The severity of infection requires an IV treatment and patient hospitalization according to the Investigator's judgment.

Exclusion Criteria:

• Previous IV antimicrobial therapy exceeding 24-hour duration during 72 hours prior to first dose.

• Any infection expected to require systemic antimicrobial agents other than study treatment(s).

• Medical history of significant hypersensitivity or allergic reaction or contraindication to the study drugs

• Medical history of central nervous system (CNS) disorders

• Medical history of myasthenia gravis.

• Medical history of C. difficile diarrhea.

• Organ-space infection.

• Complicated Intra-Abdominal Infection (cIAI)

• Chronic or underlying conditions at site of infection that may complicate the assessment of clinical response or would interfere with SSI healing.

• Underlying disease leading to deep immunosuppressive status.

• End-stage renal disease, CrCl <15 mL/min.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Agostino Gemelli	Roma		Italy

Sponsors and Collaborators

• Menarini Group

Investigators

• Principal Investigator: Stefano Margaritora, Hospital Agostino Gemelli

Study Documents (Full-Text)

• Study Protocol - Apr 5, 2019
• Statistical Analysis Plan - Sep 2, 2019

More Information

Publications

None provided.

• Responsible Party: Menarini Group
• ClinicalTrials.gov Identifier: NCT04042077
• Other Study ID Numbers: DELA-01; 2018-001082-17
• First Posted: Aug 1, 2019
• Last Update Posted: Feb 2, 2022
• Last Verified: Nov 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Menarini Group: Infection, Surgical Infection
• Additional relevant MeSH terms: Infections; Communicable Diseases; Surgical Wound Infection; Vancomycin; Tazobactam; Linezolid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tigecycline

Study Results

Participant Flow

Recruitment Details	Overall, the recruiment period lasted 13 months, since August 2019 to September 2020. The recruitment was mostly conducted at Abdominal and General surgery departments.
Pre-assignment Detail	In total, 274 patients were screened while 266 patients were randomized and treated (ITT population).

Arm/Group Title	Delafloxacin	Best Available Therapy
Arm/Group Description	Delafloxacin IV, with the option to switch to delafloxacin oral Delafloxacin: Powder for solution for infusion 300 mg or tablet 450 mg, BID, for 5 to 14 days	Cardiothoracic / related leg SSI Vancomycin IV Linezolid IV, with the option to switch to linezolid oral. In case of suspicion of Gram-negative, additional therapy shall be added as per investigator's choice Abdominal SSI Piperacillin/Tazobactam IV, OR Tigecycline IV In case of suspicion of MRSA, if the pre-selected treatment is Piperacillin/Tazobactam, additional therapy shall be added as per investigator's choice. Vancomycin: Powder for solution for infusion 15mg/kg, BID, for 5 to 14 days Linezolid: Solution for infusion or tablet, 600 mg BID, for 5 to 14 days Piperacillin/Tazobactam: Powder for solution for infusion 4/0.5 g, TID, for 5 to 14 days Tigecycline: Powder for solution for infusion 50 mg, TID, for 5 to 14 days
Period Title: Overall Study
STARTED	134	132
Vancomycin IV	0	2
Linezolid IV, With the Option to Switch to Linezolid Oral	0	8
Piperacillin/Tazobactam IV	0	68
Tigecycline IV	0	54
COMPLETED	127	127
NOT COMPLETED	7	5

Baseline Characteristics

Arm/Group Title	Delafloxacin	Best Available Therapy	Total
Arm/Group Description	Delafloxacin IV with the option to switch to OS	Vancomycin and Linezolid for cardiothoracic SSI Piperacillin/Tazobactam and Tigecycline for abdominal SSI	Total of all reporting groups
Overall Participants	134	132	266
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (13.65)	63.7 (13.71)	64.9 (13.70)
Sex: Female, Male (Count of Participants)
Female	61 45.5%	53 40.2%	114 42.9%
Male	73 54.5%	79 59.8%	152 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 2.2%	1 0.8%	4 1.5%
Not Hispanic or Latino	131 97.8%	131 99.2%	262 98.5%
Unknown or Not Reported	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 0.7%	0 0%	1 0.4%
White	133 99.3%	132 100%	265 99.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Site of infection (Count of Participants)
Abdominal SSI	124 92.5%	122 92.4%	246 92.5%
Cardiothoracic SSI	10 7.5%	10 7.6%	20 7.5%
Depth of infection (Count of Participants)
Superficial SSI	82 61.2%	79 59.8%	161 60.5%
Deep SSI	52 38.8%	53 40.2%	105 39.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Success at Test Of Cure Visit
Description	Clinical Success defined as the clinical response of "Cure" or "improved". Below the definitions: Cure: The complete resolution of all baseline signs and symptoms of SSI Improved: two or more signs and/or symptoms (but not all) were considered resolved thus the patient had improved to an extent that no additional antibiotic treatment was necessary.
Time Frame	7-14 days after last dose

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Delafloxacin	Best Available Therapy
Arm/Group Description	Delafloxacin IV with the option to switch to OS	Vancomycin and Linezolid for cardiothoracic SSI Piperacillin/Tazobactam and Tigecycline for abdominal SSI
Measure Participants	134	132
Count of Participants [Participants]	123 91.8%	119 90.2%

2. Secondary Outcome

Title	Hospital Infection Related Length of Stay (IRLOS)
Description	Length of Stay since beginning of therapy till patient stabilization and considered suitable for hospital discharge
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

CE population

Arm/Group Title	Delafloxacin	Best Available Therapy
Arm/Group Description	Delafloxacin IV with the option to switch to delafloxacin OS	Vancomycin and Linezolid for cardiothoracic SSI Piperacillin/Tazobactam and Tigecycline for abdominal SSI
Measure Participants	128	127
Mean (Standard Deviation) [hours]	130.9 (71.87)	140.3 (68.98)

3. Secondary Outcome

Title	Hospital Length of Stay (LOS)
Description	Length of Stay since Screening till actual hospital discharge
Time Frame	up to 45 days (Late Follow Up visit)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Delafloxacin	Best Available Therapy
Arm/Group Description	Delafloxacin IV with the option to switch to delafloxacin OS	Vancomycin and Linezolid for cardiothoracic SSI Piperacillin/Tazobactam and Tigecycline for abdominal SSI
Measure Participants	134	132
Mean (Standard Deviation) [hours]	178.8 (95.44)	193.5 (119.72)

4. Secondary Outcome

Title	Number of Participants Eligible to Switch to Oral Formulation According to Blinded Observer's Assessment
Description	Blinded assessment based on patient stabilization and ability to tolerate OS diet. In particular, the following details had to be met: Systolic blood pressure normal/not clinically significant abnormal No infection related tachycardia Afebrile status; body temperature <38°C for at least 24 hours* WBC count normalized/not clinically significant abnormal Patient able to tolerate PO diet/to take PO treatment and no GI absorption problem The measure counts only the participants eligible to switch, without taking into account the actually switched. Indeed, only linezolid in the BAT has an equivalent oral formulation suitable for the switch.
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Delafloxacin	Best Available Therapy
Arm/Group Description	Delafloxacin IV with the option to switch to delafloxacin OS	Vancomycin and Linezolid for cardiothoracic SSI Piperacillin/Tazobactam and Tigecycline for abdominal SSI
Measure Participants	134	132
Count of Participants [Participants]	129 96.3%	129 97.7%

5. Secondary Outcome

Title	Microbiological Response
Description	Documented or presumed eradication or persistence
Time Frame	up to 14 days (End Of Treatment visit) and 7-14 days after last dose (Test Of Cure visit)

Outcome Measure Data

Analysis Population Description

MITT population

Arm/Group Title	Delafloxacin	Best Available Therapy
Arm/Group Description	Delafloxacin IV with the option to switch to delafloxacin OS	Vancomycin and Linezolid for cardiothoracic SSI Piperacillin/Tazobactam and Tigecycline for abdominal SSI
Measure Participants	105	102
Eradicated	94 70.1%	81 61.4%
Persisted	11 8.2%	21 15.9%
Eradicated	80 59.7%	64 48.5%
Persisted	25 18.7%	38 28.8%

Adverse Events

Time Frame	Adverse events were collected for each participant from the time of ICF signature (Screening) up to to LPLV, i.e. for maximum 45 days.
Arm/Group Title	Delafloxacin		Best Available Therapy		Linezolid		Vancomycin		Piperacillin/Tazobactam		Tigecycline
Arm/Group Description	Delafloxacin IV with the option to switch to delafloxacin OS		Vancomycin and Linezolid for cardiothoracic SSI Piperacillin/Tazobactam and Tigecycline for abdominal SSI The results are not reported "per intervention" since the study was not powered to highlight difference between delafloxacin and each reference treatment. The safety analysis aimed to demonstrate that delafloxacin, among the fluoroquinolone class, is atypical showing a favourable safety profile very similar to NON-fluoroquinoles.		Linezolid IV with the option to switch to delafloxacin OS		Vancomycin IV		Piperacillin/Tazobactam IV		Tigecycline IV
All Cause Mortality
	Delafloxacin		Best Available Therapy		Linezolid		Vancomycin		Piperacillin/Tazobactam		Tigecycline
	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	4/134 (3%)		1/132 (0.8%)		0/8 (0%)		0/2 (0%)		0/68 (0%)		1/54 (1.9%)
Serious Adverse Events
	Delafloxacin		Best Available Therapy		Linezolid		Vancomycin		Piperacillin/Tazobactam		Tigecycline
	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	9/134 (6.7%)		14/132 (10.6%)		1/8 (12.5%)		0/2 (0%)		10/68 (14.7%)		3/54 (5.6%)
Cardiac disorders
angina pectoris	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
cardiac arrest	1/134 (0.7%)	1	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Gastrointestinal disorders
enterocutaneous fistula	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
ileus	1/134 (0.7%)	2	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
intestinal perforation	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
small intestinal obstruction	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
General disorders
death	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	1/54 (1.9%)	1
malaise	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Infections and infestations
abdominal wall abscess	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
clostridium difficile colitis	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
gas gangrene	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
infection	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
septic shock	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
wound infection	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Injury, poisoning and procedural complications
abdominal wound dehiscence	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
postoperative wound complications	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
wound dehiscence	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	1/54 (1.9%)	1
Nervous system disorders
cerebrovascular accident	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Respiratory, thoracic and mediastinal disorders
pleural effusion	0/134 (0%)	0	1/132 (0.8%)	1	1/8 (12.5%)	1	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
pulmonary artery thrombosis	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
pulmonary embolism	1/134 (0.7%)	1	2/132 (1.5%)	2	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	1/54 (1.9%)	1
Surgical and medical procedures
surgery	1/134 (0.7%)	1	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
Vascular disorders
deep vein thrombosis	1/134 (0.7%)	1	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	1/54 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Delafloxacin		Best Available Therapy		Linezolid		Vancomycin		Piperacillin/Tazobactam		Tigecycline
	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	22/134 (16.4%)		26/132 (19.7%)		2/8 (25%)		0/2 (0%)		18/68 (26.5%)		6/54 (11.1%)
Blood and lymphatic system disorders
anaemia	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
anemia folate deficiency	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
anemia vitamin B12 deficiency	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Iron deficiency anemia	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Endocrine disorders
thyroid mass	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Gastrointestinal disorders
diarrhoea	3/134 (2.2%)	3	3/132 (2.3%)	3	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	2/54 (3.7%)	2
nausea	2/134 (1.5%)	2	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
pancreatic calcification	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
General disorders
pyrexia	2/134 (1.5%)	2	1/132 (0.8%)	5	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	5	0/54 (0%)	0
Infections and infestations
device related infection	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	1/54 (1.9%)	1
post-operative wound infection	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
urinary tract infection	1/134 (0.7%)	1	1/132 (0.8%)	1	1/8 (12.5%)	1	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
Investigations
Hypokalaemia	3/134 (2.2%)	3	2/132 (1.5%)	3	0/8 (0%)	0	0/2 (0%)	0	2/68 (2.9%)	3	0/54 (0%)	0
hypophosphataemia	2/134 (1.5%)	2	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
Blood alkaline phosphatase increased	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	1/54 (1.9%)	1
Blood potassium decreased	0/134 (0%)	0	1/132 (0.8%)	1	1/8 (12.5%)	1	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
White blood cell count increased	2/134 (1.5%)	2	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
hypomagnaesemia	1/134 (0.7%)	1	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Metabolism and nutrition disorders
Vitamin D deficiency	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Nervous system disorders
headache	2/134 (1.5%)	2	3/132 (2.3%)	3	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	2/54 (3.7%)	2
paraesthesia	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Reproductive system and breast disorders
vaginal haemorrhage	0/134 (0%)	0	1/132 (0.8%)	1	0/8 (0%)	0	0/2 (0%)	0	1/68 (1.5%)	1	0/54 (0%)	0
Skin and subcutaneous tissue disorders
pruritus	2/134 (1.5%)	2	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0
Vascular disorders
hypertension	0/134 (0%)	0	2/132 (1.5%)	2	0/8 (0%)	0	0/2 (0%)	0	2/68 (2.9%)	2	0/54 (0%)	0
phlebitis	2/134 (1.5%)	2	0/132 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/68 (0%)	0	0/54 (0%)	0

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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.