SOLO II: Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection

• Sponsor: Melinta Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01252732
• Collaborator: (none)
• Enrollment: 1,019
• Location: 1
• Arms: 2
• Duration (Months): 30
• Patients Per Site Per Month: 34

Study Details

Study Description

Brief Summary

The purpose of this Phase 3 trial is to evaluate the efficacy, safety, and tolerability of oritavancin in ABSSSIs, including those caused by MRSA and to evaluate the potential economic benefit of oritavancin administered as a single 1200 mg IV dose.

Condition or Disease	Intervention/Treatment	Phase
Wound Infection; Abscess; Systemic Inflammation; Cellulitis	Drug: Single-Dose IV Oritavancin Diphosphate; Drug: IV Vancomycin	Phase 3

Detailed Description

This is a Phase 3, multicenter, randomized, double-blind, parallel, comparative efficacy and safety study of single-dose IV oritavancin/IV placebo versus IV vancomycin for 7 to 10 days in adults with acute bacterial skin and skin structure infection (ABSSSI) suspected or proven to be caused by Gram-positive pathogens. Approximately 960 patients will be randomized at 100 centers globally.

In addition, this study will characterize the PK and PK/PD properties of a single 1200 mg IV dose of oritavancin and evaluate the potential health economic benefits offered by this dosing strategy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1019 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Single-Dose IV Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection (SOLO II)
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-Dose IV Oritavancin Diphosphate	Drug: Single-Dose IV Oritavancin Diphosphate; Intravenous oritavancin and IV placebo or IV vancomycin will be administered for a minimum of 7 days up to a maximum of 10 days.
Active Comparator: IV Vancomycin	Drug: IV Vancomycin; Intravenous oritavancin and IV placebo or IV vancomycin will be administered for a minimum of 7 days up to a maximum of 10 days.

Outcome Measures

Primary Outcome Measures

1. Early Clinical Response [48-72 hours after the initation of study therapy]

   Clinical response at the ECE visit (48-72 hours following initiation of study drug administration). Early clinical response was defined as a composite outcome based on, cessation of spreading or reduction in the size of baseline lesion, absence of fever and no rescue antibiotic medication.

Secondary Outcome Measures

1. Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint) [7 to 14 days after end of therapy]

   Compared the clinical efficacy at the Post Therapy Evaluation of Oritavancin and Vancomycin based on the Investigator examination of the signs and symptoms of the primary ABSSSI; Investigator assessment of clinical cure is complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics is needed

2. >= 20% Reduction in Lesion Area [48-72 hours after the initation of study therapy]

   Clinical response at the ECE visit (48-72 hours following initiation of study drug administration) based on changes in ABSSSI lesion size measurements from baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Subjects may be included in the study if they meet all of the following inclusion criteria:

1. Males or females ≥18 years old

2. Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 5 days of IV therapy

3. An ABSSSI includes one of the following infections Wound infections, Cellulitis/erysipelas, Major cutaneous abscess

4. ABSSSI must present with at least 2 signs and symptoms

5. Able to give informed consent and willing to comply with all required study procedures

Exclusion Criteria:

Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

1. Prior systemic or topical antibacterial therapy with activity against suspected or proven Gram-positive pathogens within the preceding 14 days

• The causative Gram-positive pathogen(s) isolated from the ABSSSI site is resistant in vitro to the antibacterial(s) that was administered with documented clinical progression, or

• Documented failure to previous ABSSSI antibiotic therapy is available. Documentation of treatment failure must be recorded

• Patient received a single dose of a short acting antibacterial therapy three or more days before randomization

1. Infections associated with, or in close proximity to, a prosthetic device

2. Severe sepsis or refractory shock

3. Known or suspected bacteremia at time of screening

4. ABSSSI due to or associated with any of the following:

• Infections suspected or documented to be caused by Gram-negative pathogens -- Wound infections (surgical or traumatic) and abscesses with only Gram-negative pathogens

• Diabetic foot infections

• Concomitant infection at another site not including a secondary ABSSSI lesion

• Infected burns

• A primary infection secondary to a pre-existing skin disease with associated inflammatory changes

• Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease

• Any evolving necrotizing process gangrene or infection suspected or proven to be caused by Clostridium species

• Infections known to be caused by a Gram-positive organism with a vancomycin MIC

2 μg/mL or clinically failing prior therapy with glycopeptides

• Catheter site infections

1. Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria

2. Currently receiving chronic systemic immunosuppressive therapy

3. AIDS with CD4 count < 200 cells/mm3

4. Neutropenia

5. Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI

6. Women who are pregnant or nursing

7. History of immune-related hypersensitivity reaction to glycopeptides

8. Patients that require anticoagulant monitoring with an aPTT

9. Contraindication to vancomycin

10. Patients unwilling to forego blood and/or blood product donation

11. Treatment with investigational medicinal product within 30 days before enrollment and for the duration of the study

12. Investigational device present, or removed <30 days before enrollment, or presence of device-related infection

13. Patients unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study

14. Severe hepatic disease

15. Presence of hyperuricemia

16. Unwilling to refrain from chronic use of any medication with antipyretic properties

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sharp Grossmont Hospital	La Mesa	California	United States	91942

Sponsors and Collaborators

• Melinta Therapeutics, Inc.

Investigators

• Principal Investigator: G. Ralph Corey, MD, Duke Clinical Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melinta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01252732
• Other Study ID Numbers: TMC-ORI-10-02
• First Posted: Dec 3, 2010
• Last Update Posted: May 5, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Melinta Therapeutics, Inc.: ABSSSI; Skin Infection; Abscess
• Additional relevant MeSH terms: Infections; Communicable Diseases; Wound Infection; Abscess; Cellulitis; Inflammation; Vancomycin; Oritavancin

Study Results

Participant Flow

Arm/Group Title	Single-Dose 1200 mg Oritavancin	Vancomycin
Arm/Group Description	Single 1200 mg IV Dose of Oritavancin Diphosphate administered as first infusion followed by IV placebo administered twice daily for a minimum of 7 days up to a maximum of 10 days.	IV Vancomycin, 1g or 15mg/kg administered twice daily for a minimum of 7 days up to a maximum of 10 days.
Period Title: Overall Study
STARTED	509	510
Modified Intent to Treat Population	503	502
COMPLETED	455	446
NOT COMPLETED	54	64

Baseline Characteristics

Arm/Group Title	Single-Dose 1200 mg Oritavancin	Vancomycin	Total
Arm/Group Description	Single 1200 mg IV Dose of Oritavancin Diphosphate administered as first infusion followed by IV placebo administered twice daily for a minimum of 7 days up to a maximum of 10 days.	IV Vancomycin, 1g or 15mg/kg administered twice daily for a minimum of 7 days up to a maximum of 10 days.	Total of all reporting groups
Overall Participants	503	502	1005
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.0 (13.40)	44.4 (14.29)	44.7 (13.85)
Sex: Female, Male (Count of Participants)
Female	165 32.8%	159 31.7%	324 32.2%
Male	338 67.2%	343 68.3%	681 67.8%

Outcome Measures

1. Primary Outcome

Title	Early Clinical Response
Description	Clinical response at the ECE visit (48-72 hours following initiation of study drug administration). Early clinical response was defined as a composite outcome based on, cessation of spreading or reduction in the size of baseline lesion, absence of fever and no rescue antibiotic medication.
Time Frame	48-72 hours after the initation of study therapy

Outcome Measure Data

Analysis Population Description

Modified intent to treat (mITT) population consisting of all patients randomized into the trial and received any study drug.

Arm/Group Title	Single-Dose 1200 mg Oritavancin	Vancomycin
Arm/Group Description	Single 1200 mg IV Dose of Oritavancin Diphosphate administered as first infusion followed by IV placebo administered twice daily for a minimum of 7 days up to a maximum of 10 days.	IV Vancomycin, 1g or 15mg/kg administered twice daily for a minimum of 7 days up to a maximum of 10 days.
Measure Participants	503	502
Success	403 80.1%	416 82.9%
Failure	100 19.9%	86 17.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Single-Dose 1200 mg Oritavancin, Vancomycin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The non-inferiority hypothesis test is a one sided hypothesis test performed at the 2.5% level of significance. If the lower limit of the two-sided 95% CI for the difference in response rates in the mITT population is greater than -10% the NI of oritavancin to vancomycin is concluded.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -7.5 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint)
Description	Compared the clinical efficacy at the Post Therapy Evaluation of Oritavancin and Vancomycin based on the Investigator examination of the signs and symptoms of the primary ABSSSI; Investigator assessment of clinical cure is complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics is needed
Time Frame	7 to 14 days after end of therapy

Outcome Measure Data

Analysis Population Description

Modified intent to treat (mITT) population consisting of all patients randomized into the trial and received any study drug.

Arm/Group Title	Single-Dose 1200 mg Oritavancin	Vancomycin
Arm/Group Description	Single 1200 mg IV Dose of Oritavancin Diphosphate administered as first infusion followed by IV placebo administered twice daily for a minimum of 7 days up to a maximum of 10 days.	IV Vancomycin, 1g or 15mg/kg administered twice daily for a minimum of 7 days up to a maximum of 10 days.
Measure Participants	503	502
Clinical Cure	416 82.7%	404 80.5%
Clinical Failure	87 17.3%	98 19.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Single-Dose 1200 mg Oritavancin, Vancomycin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The non-inferiority hypothesis test is a one sided hypothesis test performed at the 2.5% level of significance. If the lower limit of the two-sided 95% CI for the difference in response rates in the mITT population is greater than -10% the NI of oritavancin to vancomycin is concluded.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -2.6 to 7.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	>= 20% Reduction in Lesion Area
Description	Clinical response at the ECE visit (48-72 hours following initiation of study drug administration) based on changes in ABSSSI lesion size measurements from baseline.
Time Frame	48-72 hours after the initation of study therapy

Outcome Measure Data

Analysis Population Description

Modified intent to treat (mITT) population consisting of all patients randomized into the trial and received any study drug.

Arm/Group Title	Single-Dose 1200 mg Oritavancin	Vancomycin
Arm/Group Description	Single 1200 mg IV Dose of Oritavancin Diphosphate administered as first infusion followed by IV placebo administered twice daily for a minimum of 7 days up to a maximum of 10 days.	IV Vancomycin, 1g or 15mg/kg administered twice daily for a minimum of 7 days up to a maximum of 10 days.
Measure Participants	503	502
Success	432 85.9%	428 85.3%
Failure	71 14.1%	74 14.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Single-Dose 1200 mg Oritavancin, Vancomycin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The non-inferiority hypothesis test is a one sided hypothesis test performed at the 2.5% level of significance. If the lower limit of the two-sided 95% CI for the difference in response rates in the mITT population is greater than -10% the NI of oritavancin to vancomycin is concluded.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -3.7 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Begins from the time the patient provided informed consent through to the last follow up visit at 60 (+7) days.
Adverse Event Reporting Description	Additional Description Adverse events were analysed in the safety population consisting of all patients who received any study drug. The analysis was performed according to the actual treatment that the patient received.
Arm/Group Title	Single-Dose 1200 mg Oritavancin		Vancomycin
Arm/Group Description	Single 1200 mg IV Dose of Oritavancin Diphosphate administered as first infusion followed by IV placebo administered twice daily for a minimum of 7 days up to a maximum of 10 days.		IV Vancomycin, 1g or 15mg/kg administered twice daily for a minimum of 7 days up to a maximum of 10 days.
All Cause Mortality
	Single-Dose 1200 mg Oritavancin		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Single-Dose 1200 mg Oritavancin		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/503 (4.4%)		23/502 (4.6%)
Cardiac disorders
Cardiac Failure Congestive	1/503 (0.2%)		1/502 (0.2%)
Electromechanical dissociation	1/503 (0.2%)		0/502 (0%)
Acute Myocardial Infarction	0/503 (0%)		2/502 (0.4%)
Myocardial Ischaemia	0/503 (0%)		1/502 (0.2%)
Gastrointestinal disorders
Mouth Ulceration	1/503 (0.2%)		0/502 (0%)
Rectal Hemorrhage	1/503 (0.2%)		0/502 (0%)
Constipation	0/503 (0%)		1/502 (0.2%)
Oesophagitis	0/503 (0%)		1/502 (0.2%)
General disorders
Chest Pain	1/503 (0.2%)		0/502 (0%)
Non-cardiac Chest Pain	0/503 (0%)		1/502 (0.2%)
Pyrexia	0/503 (0%)		1/502 (0.2%)
Immune system disorders
Anaphylactoid Reaction	0/503 (0%)		1/502 (0.2%)
Infections and infestations
Cellulitis	6/503 (1.2%)		4/502 (0.8%)
Osteomyelitis	4/503 (0.8%)		0/502 (0%)
Bronchitis	1/503 (0.2%)		0/502 (0%)
Gangrene	1/503 (0.2%)		0/502 (0%)
Infection	1/503 (0.2%)		0/502 (0%)
Necrotizing Fasciitis	1/503 (0.2%)		0/502 (0%)
Pneumonia	1/503 (0.2%)		0/502 (0%)
Wound Infection Staphylococcal	1/503 (0.2%)		0/502 (0%)
Abscess Bacterial	0/503 (0%)		1/502 (0.2%)
Arthritis Bacterial	0/503 (0%)		1/502 (0.2%)
Extradural Abscess	0/503 (0%)		1/502 (0.2%)
Intervertebral Discitis	0/503 (0%)		1/502 (0.2%)
Lower Respiratory Tract Infection	0/503 (0%)		1/502 (0.2%)
Skin Bacterial Infection	0/503 (0%)		1/502 (0.2%)
Skin Infection	0/503 (0%)		2/502 (0.4%)
Injury, poisoning and procedural complications
Clavicle Fracture	0/503 (0%)		1/502 (0.2%)
Metabolism and nutrition disorders
Hyperglycemia	1/503 (0.2%)		0/502 (0%)
Dehydration	0/503 (0%)		1/502 (0.2%)
Hyponatraemia	0/503 (0%)		1/502 (0.2%)
Metabolic Acidosis	0/503 (0%)		1/502 (0.2%)
Musculoskeletal and connective tissue disorders
Tenosynovitis	1/503 (0.2%)		0/502 (0%)
Nervous system disorders
Convulsion	1/503 (0.2%)		1/502 (0.2%)
Headache	0/503 (0%)		1/502 (0.2%)
Psychiatric disorders
Psychotic Disorder	0/503 (0%)		1/502 (0.2%)
Suicide Attempt	0/503 (0%)		1/502 (0.2%)
Renal and urinary disorders
Renal Failure	0/503 (0%)		1/502 (0.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/503 (0.2%)		2/502 (0.4%)
Skin and subcutaneous tissue disorders
Angioedema	1/503 (0.2%)		0/502 (0%)
Leukocytoplastic Vasculitis	1/503 (0.2%)		0/502 (0%)
Skin Ulcer	0/503 (0%)		1/502 (0.2%)
Other (Not Including Serious) Adverse Events
	Single-Dose 1200 mg Oritavancin		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	272/503 (54.1%)		265/502 (52.8%)
Cardiac disorders
tachycardia	15/503 (3%)		7/502 (1.4%)
Gastrointestinal disorders
nausea	45/503 (8.9%)		60/502 (12%)
vomiting	22/503 (4.4%)		28/502 (5.6%)
constipation	14/503 (2.8%)		17/502 (3.4%)
diarrhea	13/503 (2.6%)		15/502 (3%)
General disorders
infusion site phlebitis	16/503 (3.2%)		5/502 (1%)
pyrexia	15/503 (3%)		11/502 (2.2%)
infusion site extravasation	15/503 (3%)		10/502 (2%)
Infections and infestations
cellulitis	17/503 (3.4%)		15/502 (3%)
abscess limb	14/503 (2.8%)		8/502 (1.6%)
Investigations
alanine aminotransferase increased	16/503 (3.2%)		10/502 (2%)
aspartate aminotransferase increased	11/503 (2.2%)		11/502 (2.2%)
Nervous system disorders
headache	35/503 (7%)		28/502 (5.6%)
dizziness	11/503 (2.2%)		11/502 (2.2%)
Skin and subcutaneous tissue disorders
pruritus	13/503 (2.6%)		29/502 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.