SOLO II: Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection
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 |
---|---|---|
|
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
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
- 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
- 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
- >= 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
Inclusion Criteria:
Subjects may be included in the study if they meet all of the following inclusion criteria:
-
Males or females ≥18 years old
-
Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 5 days of IV therapy
-
An ABSSSI includes one of the following infections Wound infections, Cellulitis/erysipelas, Major cutaneous abscess
-
ABSSSI must present with at least 2 signs and symptoms
-
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:
- 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
-
Infections associated with, or in close proximity to, a prosthetic device
-
Severe sepsis or refractory shock
-
Known or suspected bacteremia at time of screening
-
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
-
Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria
-
Currently receiving chronic systemic immunosuppressive therapy
-
AIDS with CD4 count < 200 cells/mm3
-
Neutropenia
-
Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI
-
Women who are pregnant or nursing
-
History of immune-related hypersensitivity reaction to glycopeptides
-
Patients that require anticoagulant monitoring with an aPTT
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Contraindication to vancomycin
-
Patients unwilling to forego blood and/or blood product donation
-
Treatment with investigational medicinal product within 30 days before enrollment and for the duration of the study
-
Investigational device present, or removed <30 days before enrollment, or presence of device-related infection
-
Patients unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study
-
Severe hepatic disease
-
Presence of hyperuricemia
-
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.- TMC-ORI-10-02
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
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
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 |
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 |
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
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.
Results Point of Contact
Name/Title | Karen Fusaro |
---|---|
Organization | Melinta Therapeutics, Inc. |
Phone | 6098270956 |
kfusaro@melinta.com |
- TMC-ORI-10-02