Single Dose vs. Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

• Sponsor: Durata Therapeutics Inc., an affiliate of Allergan plc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02127970
• Collaborator: (none)
• Enrollment: 698
• Locations: 78
• Arms: 2
• Actual Duration (Months): 10.7
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

To compare the efficacy of treatment with a single dose of dalbavancin 1500 mg to treatment with a two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in participants with known or suspected Gram-positive acute bacterial skin and skin structure infections (ABSSSI) at 48 -72 hours after initiation of treatment.

Condition or Disease	Intervention/Treatment	Phase
Abscess; Wound Infection; Surgical Site Infection; Cellulitis	Drug: Dalbavancin; Drug: Dalbavancin-matching Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 698 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Double-Blind, Multicenter, Randomized Study to Compare the Efficacy and Safety of Single Dose Dalbavancin to a Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections
• Actual Study Start Date: Apr 18, 2014
• Actual Primary Completion Date: Mar 11, 2015
• Actual Study Completion Date: Mar 11, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-Dose Dalbavancin Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Drug: Dalbavancin; Dalbavancin IV infusion over 30 minutes.; Other Names: DALVANCE® ; Drug: Dalbavancin-matching Placebo; Dalbavancin-matching placebo IV infusion over 30 minutes.
Experimental: Two-Dose Dalbavancin Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.	Drug: Dalbavancin; Dalbavancin IV infusion over 30 minutes.; Other Names: DALVANCE®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Were Clinical Responders 48-72 Hours After the Initiation of Study Drug [Up to 48-72 hours after the initiation of study drug]

   Clinical responder was defined as a participant who was alive and had received no rescue therapy for acute bacterial skin and skin structure infection (ABSSSI) prior to the 48-72 hour infection site assessment (if an antibiotic has been given for another reason, the participant will not be considered a non-responder for this reason); and examination of the participant's ABSSSI lesion demonstrates a decrease of ≥ 20% in lesion area (calculated as the longest length multiplied by the longest perpendicular width) relative to the baseline measurement.

Secondary Outcome Measures

1. Percentage of Participants by Clinical Status at End of Treatment (EOT) and Final Visit (FV) [End of Treatment (Day 14-15 after the initiation of study drug) and Final Visit (28 ±2 days after the initiation of study drug)]

   Clinical Success is defined as follows: For evaluation at EOT visit, lesion area must be decreased by ≥80% from baseline and at FV lesion area must be decreased by ≥90% from baseline; Temperature is ≤37.6°C; Local signs of tenderness to palpation and swelling/induration are no worse than mild; For evaluation at EOT visit, local signs of fluctuance and localized heat/warmth must be improved from baseline and no worse than mild, and at FV local signs of fluctuance and localized heat/warmth must be absent; for participants with a wound infection the severity of purulent drainage is improved and no worse than mild relative to baseline. Clinical Failure is defined as the opposite to success or if the participant died during the study period up to visit or received study therapy for ABSSSI beyond the protocol treatment period. Clinical status is Indeterminate if any of the data needed to determine clinical success or clinical failure were missing.

Other Outcome Measures

1. Percentage of Participants by Clinical Status Based on Localized Fluctuance and Heat/Warmth at End of Treatment (EOT) [EOT (Day 14-15)]

   Clinical Success was defined as localized fluctuance and heat/warmth that if present at Baseline must be improved and no worse than mild. Clinical Failure was defined as the opposite to success. Clinical status was Indeterminate if any of the data needed to determine clinical success or clinical failure were missing.

2. Percentage of Participants by Investigator Assessment of Clinical Outcome [Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)]

   A successful outcome was based on resolution or improvement of all signs and symptoms of the infection to such an extent that no further antibacterial treatment was given. An unsuccessful outcome was the opposite of successful. An Indeterminate outcome was defined as any of the data needed to determine a successful or unsuccessful outcome were missing.

3. Percentage of Participants Achieving Clinical Outcome of Success Based on Key Target Pathogen at Baseline [Day 3-4 and EOT (Day 14-15)]

   A successful outcome was based on resolution or improvement of all signs and symptoms of the infection to such an extent that no further antibacterial treatment was given.

4. Percentage of Participants With Complete Resolution of Local Signs of Infection [Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)]

   Resolution of Local Signs of Infection that include absence of purulence/drainage, erythema, heat/localized warmth, pain/tenderness to palpation, fluctuance, and swelling/induration.

5. Change From Baseline in Participant's Assessment of Pain [Baseline (Day 0) to Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 + /- 2 days)]

   Using the Brief Pain Inventory Scale, participants rated their pain "right now" on a scale where: 0=no pain to 10=pain as bad as you can imagine. A negative change from Baseline indicated improvement.

6. Percentage of Participants by Resource Utilization Categories [Final Visit (Day 28 +/- 2 days)]

   Resource Utilization Categories included: Any additional visits (including urgent care), Any additional procedures, Any additional tests, Any home visits or nursing care and Any ER Visits. The percentage of participants in each category is reported.

7. Percentage of Participants by Skin and Soft Tissue Infection-Convenience (SSTI-C) Questionnaire: Overall Satisfaction Response [EOT (Day 14-15)]

   The SSTI-C Questionnaire is an 11-item self-reported questionnaire that measures subjective experiences of the participant. One of the items assessed was overall satisfaction with treatment. Participants answered the question: "Overall, how satisfied were you with your antibiotic treatment?" using one of the following responses: Extremely satisfied, Moderately satisfied, Not at all satisfied, Slightly satisfied and Very satisfied. The percentage of participants in each category is reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female participants 18 - 85 years of age.

• Signed and dated informed consent document.

• Major abscess, surgical site infection, traumatic wound infection or cellulitis suspected or confirmed to be caused by Gram-positive bacteria.

• At least two (2) local signs and symptoms of acute bacterial skin and skin structure infection (ABSSSI and at least one systemic sign of infection.

• Participant willing and able to comply with study procedures.

Exclusion Criteria:

• A contra-indication to dalbavancin.

• Pregnant or nursing females.

• Sustained shock.

• Participation in another study of an investigational drug or device within 30 days.

• Receipt of a systemically or topically administered antibiotic with a Gram-positive spectrum that achieves therapeutic concentrations in the serum or at the site of the ABSSSI within 14 days prior to randomization. An exception is allowed for participants receiving a single dose of a short-acting (half-life ≤ 12 hours) antibacterial drug prior to randomization; up to 25% of participants may have received such therapy.

• Infection due to an organism known prior to study entry to be resistant to dalbavancin or vancomycin (vancomycin MIC (minimum inhibitory concentration) >8 μg/mL).

• Evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis; endovascular infection, such as clinical and/or echocardiographic evidence of endocarditis or septic thrombophlebitis.

• Infections caused exclusively by Gram-negative bacteria (without Gram-positive bacteria present) and infections caused by fungi, whether alone or in combination with a bacterial pathogen.

• Venous catheter entry site infection.

• Infections involving a diabetic foot ulceration, perirectal abscess or a decubitus ulcer.

• Participant with an infected device, even if the device is removed. Examples include infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis, hemodialysis catheter, implantable pacemaker or defibrillator, intra-aortic balloon pump, left ventricular assist device, a peritoneal dialysis catheter, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.

• Gram-negative bacteremia, even in the presence of Gram-positive infection or Gram-positive bacteremia. Note: If a Gram-negative bacteremia develops during the study, or is subsequently found to have been present at Baseline, the participant should be removed from study treatment and receive appropriate antibiotic(s) to treat the Gram-negative bacteremia. Such participants must have an end of treatment (EOT) visit performed within 3 calendar days after discontinuing study medication but are required to have AEs (adverse events) reported through the Final Visit.

• Participants whose ABSSSI is the result of having sustained full or partial thickness burns.

• Participants with an infection involving a limb with evidence of critical ischemia of an affected limb defined as any of the following criteria: absent or abnormal Doppler wave forms, toe blood pressure of <45 mm Hg, ankle brachial index <0.5, and/ or critical ischemia as assessed by a vascular surgeon.

• Participants with ABSSSI such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure.

• Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study.

• Anticipated need of antibiotic therapy for longer than 14 days.

• Participants who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI.

• More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically unable to be performed at the bedside) for the ABSSSI, or participants who are expected to require more than 2 such interventions.

• Medical conditions in which chronic inflammation may preclude assessment of clinical response to therapy even after successful treatment (e.g., chronic stasis dermatitis of the lower extremity).

• Absolute neutrophil count <500 cells/mm^3.

• Known or suspected human immunodeficiency virus (HIV) infected participants with a CD4 (cluster of differentiation 4) cell count <200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.

• Participants with a recent bone marrow transplant (in post-transplant hospital stay).

• Participants receiving oral steroids >20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation.

• Participants with a rapidly fatal illness, who are not expected to survive for 3 months.

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participants inappropriate for entry into this study.

• Prior participation in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	110	Montgomery	Alabama	United States	36106
2	103	Anaheim	California	United States	92804
3	117	Long Beach	California	United States	90806
4	106	Long Beach	California	United States	90813
5	118	Modesto	California	United States	95350
6	104	San Diego	California	United States	92120
7	113	San Diego	California	United States	92120
8	115	San Diego	California	United States	92120
9	116	San Diego	California	United States	92120
10	108	Stockton	California	United States	95204
11	105	Sylmar	California	United States	91342
12	112	Washington	District of Columbia	United States	20037
13	107	Orlando	Florida	United States	32806
14	120	Saint Cloud	Florida	United States	34769
15	114	Augusta	Georgia	United States	30909
16	122	Columbus	Georgia	United States	31904
17	125	Savannah	Georgia	United States	31405
18	119	Eunice	Louisiana	United States	70535
19	101	Springfield	Massachusetts	United States	01199
20	109	Detroit	Michigan	United States	48202
21	121	Butte	Montana	United States	59701
22	123	Omaha	Nebraska	United States	68131
23	111	Toledo	Ohio	United States	43608
24	126	Franklin	Tennessee	United States	37064
25	127	Smyrna	Tennessee	United States	37167
26	802	Sofia		Bulgaria	1000
27	800	Sofia		Bulgaria	1431
28	801	Sofia		Bulgaria	1606
29	200	Zagreb		Croatia	10000
30	201	Zagreb		Croatia	10000
31	253	Tallinn		Estonia	10318
32	252	Tallinn		Estonia	13419
33	251	Tartu		Estonia	51014
34	302	Kutaisi		Georgia	4600
35	303	Tbilisi		Georgia	0144
36	300	Tbilisi		Georgia	0160
37	301	Tbilisi		Georgia	0160
38	352	Debrecen		Hungary	4012
39	353	Kaposvar		Hungary	7400
40	354	Pecs		Hungary	7632
41	351	Szeged		Hungary	6720
42	402	Daugavpils		Latvia	LV-5417
43	401	Liepaja		Latvia	LV-3414
44	403	Rezekne		Latvia	LV-4601
45	400	Riga		Latvia	LV-1002
46	404	Riga		Latvia	LV-1038
47	501	Cluj-Napoca	Cluj County	Romania	400006
48	502	Bucharest		Romania	030303
49	500	Bucharest		Romania	041915
50	503	Bucharest		Romania	42122
51	555	Vsevolozhsk	Leningrad Region	Russian Federation	188643
52	557	Irkutsk		Russian Federation	664079
53	552	Moscow		Russian Federation	111539
54	554	Moscow		Russian Federation	111539
55	553	Novosibirsk		Russian Federation	630051
56	551	St. Petersburg		Russian Federation	198099
57	556	Tomsk		Russian Federation	634063
58	600	Belgrade		Serbia	11000
59	601	Belgrade		Serbia	11000
60	603	Nis		Serbia	18000
61	602	Novi Sad		Serbia	21000
62	756	Breyten		South Africa	2330
63	760	Cape Town		South Africa	7530
64	752	Dundee		South Africa	3000
65	755	Johannesburg		South Africa	2113
66	751	Middleburg		South Africa	1055
67	758	Port Elizabeth		South Africa	6014
68	757	Pretoria		South Africa	0040
69	753	Pretoria		South Africa	0084
70	759	Pretoria		South Africa	0183
71	754	Worcester		South Africa	6850
72	700	Cherkasy		Ukraine	18009
73	704	Dnipropetrovsk		Ukraine	49005
74	706	Ivano-Frankivsk		Ukraine	76012
75	701	Ivano-Frankivsk		Ukraine	76025
76	705	Kharkiv		Ukraine	61037
77	703	Lviv		Ukraine	79059
78	702	Zaporizhzhya		Ukraine	69032

Sponsors and Collaborators

• Durata Therapeutics Inc., an affiliate of Allergan plc

Investigators

• Study Director: Urania Rappo, MD, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Durata Therapeutics Inc., an affiliate of Allergan plc
• ClinicalTrials.gov Identifier: NCT02127970
• Other Study ID Numbers: DUR001-303
• First Posted: May 1, 2014
• Last Update Posted: Sep 28, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Infections; Communicable Diseases; Surgical Wound Infection; Wound Infection; Cellulitis; Dalbavancin; Teicoplanin

Study Results

Participant Flow

Pre-assignment Detail	A total of 698 participants were randomly assigned in a 1:1 ratio to the following treatment groups: Single-dose dalbavancin group, received a single dose of dalbavancin intravenous (IV) on Day 1, and a matching placebo IV on Day 8; Two-dose dalbavancin group, received dalbavancin IV on Day 1 and Day 8.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Period Title: Overall Study
STARTED	349	349
COMPLETED	323	322
NOT COMPLETED	26	27

Baseline Characteristics

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin	Total
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.	Total of all reporting groups
Overall Participants	349	349	698
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.0 (14.83)	48.3 (14.74)	48.2 (14.78)
Sex: Female, Male (Count of Participants)
Female	145 41.5%	146 41.8%	291 41.7%
Male	204 58.5%	203 58.2%	407 58.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Were Clinical Responders 48-72 Hours After the Initiation of Study Drug
Description	Clinical responder was defined as a participant who was alive and had received no rescue therapy for acute bacterial skin and skin structure infection (ABSSSI) prior to the 48-72 hour infection site assessment (if an antibiotic has been given for another reason, the participant will not be considered a non-responder for this reason); and examination of the participant's ABSSSI lesion demonstrates a decrease of ≥ 20% in lesion area (calculated as the longest length multiplied by the longest perpendicular width) relative to the baseline measurement.
Time Frame	Up to 48-72 hours after the initiation of study drug

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	349	349
Number [percentage of participants]	81.4 23.3%	84.2 24.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Single-Dose Dalbavancin, Two-Dose Dalbavancin
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority hypothesis test was to be a one-sided hypothesis test performed at the 2.5% level of significance. If the lower limit of the 95% CI for the difference in responder rates is greater than -10%, then the single-dose dalbavancin regimen was to be declared non-inferior to the two dose dalbavancin regimen.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -8.5 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	For the difference in clinical responder rates (single-dose group minus two dose group), the 95% CI was calculated using the Miettinen and Nurminen method without adjustment.

2. Secondary Outcome

Title	Percentage of Participants by Clinical Status at End of Treatment (EOT) and Final Visit (FV)
Description	Clinical Success is defined as follows: For evaluation at EOT visit, lesion area must be decreased by ≥80% from baseline and at FV lesion area must be decreased by ≥90% from baseline; Temperature is ≤37.6°C; Local signs of tenderness to palpation and swelling/induration are no worse than mild; For evaluation at EOT visit, local signs of fluctuance and localized heat/warmth must be improved from baseline and no worse than mild, and at FV local signs of fluctuance and localized heat/warmth must be absent; for participants with a wound infection the severity of purulent drainage is improved and no worse than mild relative to baseline. Clinical Failure is defined as the opposite to success or if the participant died during the study period up to visit or received study therapy for ABSSSI beyond the protocol treatment period. Clinical status is Indeterminate if any of the data needed to determine clinical success or clinical failure were missing.
Time Frame	End of Treatment (Day 14-15 after the initiation of study drug) and Final Visit (28 ±2 days after the initiation of study drug)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	349	349
EOT; Clinical Success	84.0 24.1%	84.8 24.3%
EOT; Clinical Failure	12.0 3.4%	10.3 3%
EOT; Indeterminate	4.0 1.1%	4.9 1.4%
FV; Clinical Success	84.5 24.2%	85.1 24.4%
FV; Clinical Failure	8.0 2.3%	7.2 2.1%
FV; Indeterminate	7.4 2.1%	7.3 2.1%

3. Other Pre-specified Outcome

Title	Percentage of Participants by Clinical Status Based on Localized Fluctuance and Heat/Warmth at End of Treatment (EOT)
Description	Clinical Success was defined as localized fluctuance and heat/warmth that if present at Baseline must be improved and no worse than mild. Clinical Failure was defined as the opposite to success. Clinical status was Indeterminate if any of the data needed to determine clinical success or clinical failure were missing.
Time Frame	EOT (Day 14-15)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	349	349
Clinical Success	84.8 24.3%	85.4 24.5%
Clinical Failure	7.7 2.2%	6.9 2%
Indeterminate	7.4 2.1%	7.7 2.2%

4. Other Pre-specified Outcome

Title	Percentage of Participants by Investigator Assessment of Clinical Outcome
Description	A successful outcome was based on resolution or improvement of all signs and symptoms of the infection to such an extent that no further antibacterial treatment was given. An unsuccessful outcome was the opposite of successful. An Indeterminate outcome was defined as any of the data needed to determine a successful or unsuccessful outcome were missing.
Time Frame	Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	347	344
Successful Outcome (Day 3-4)	93.4 26.8%	93.0 26.6%
Unsuccessful Outcome (Day 3-4)	0.3 0.1%	0.9 0.3%
Indeterminate (Day 3-4)	6.3 1.8%	6.1 1.7%
Successful Outcome (Day 8)	92.2 26.4%	93.3 26.7%
Unsuccessful Outcome (Day 8)	0.6 0.2%	0.3 0.1%
Indeterminate (Day 8)	7.2 2.1%	6.4 1.8%
Successful Outcome (EOT)	92.5 26.5%	92.7 26.6%
Unsuccessful Outcome (EOT)	2.9 0.8%	1.5 0.4%
Indeterminate (EOT)	4.6 1.3%	5.8 1.7%
Successful Outcome (Final Visit)	90.2 25.8%	91.0 26.1%
Unsuccessful Outcome (Final Visit)	2.6 0.7%	1.7 0.5%
Indeterminate (Final Visit)	7.2 2.1%	7.3 2.1%

5. Other Pre-specified Outcome

Title	Percentage of Participants Achieving Clinical Outcome of Success Based on Key Target Pathogen at Baseline
Description	A successful outcome was based on resolution or improvement of all signs and symptoms of the infection to such an extent that no further antibacterial treatment was given.
Time Frame	Day 3-4 and EOT (Day 14-15)

Outcome Measure Data

Analysis Population Description

Microbiological Intent-to-treat (MicroITT) Population included all ITT participants who had at least 1 Gram-positive bacterial pathogen isolated at Baseline. Number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	210	220
Staphylococcus aureus (Day 3-4)	88.5 25.4%	85.3 24.4%
Streptococcus agalactiae (Day 3-4)	100.0 28.7%	66.7 19.1%
Streptococcus anginosus group (Day 3-4)	93.9 26.9%	100.0 28.7%
Streptococcus dysgalactiae (Day 3-4)	100.0 28.7%	100.0 28.7%
Streptococcus pyogenes (Day 3-4)	100.0 28.7%	81.8 23.4%
Enterococcus faecalis (Day 3-4)	100.0 28.7%	80.0 22.9%
Staphylococcus aureus (EOT)	87.8 25.2%	91.7 26.3%
Streptococcus agalactiae (EOT)	83.3 23.9%	83.3 23.9%
Streptococcus anginosus group (EOT)	81.8 23.4%	89.5 25.6%
Streptococcus dysgalactiae (EOT)	100.0 28.7%	100.0 28.7%
Streptococcus pyogenes (EOT)	92.9 26.6%	81.8 23.4%
Enterococcus faecalis (EOT)	100.0 28.7%	100.0 28.7%

6. Other Pre-specified Outcome

Title	Percentage of Participants With Complete Resolution of Local Signs of Infection
Description	Resolution of Local Signs of Infection that include absence of purulence/drainage, erythema, heat/localized warmth, pain/tenderness to palpation, fluctuance, and swelling/induration.
Time Frame	Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	349	349
Day 3-4	1.9 0.5%	1.5 0.4%
Day 8	22.3 6.4%	21.1 6%
EOT Visit	56.3 16.1%	56.2 16.1%
Final Visit	85.8 24.6%	89.8 25.7%

7. Other Pre-specified Outcome

Title	Change From Baseline in Participant's Assessment of Pain
Description	Using the Brief Pain Inventory Scale, participants rated their pain "right now" on a scale where: 0=no pain to 10=pain as bad as you can imagine. A negative change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) to Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 + /- 2 days)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	349	349
Baseline	7.7 (2.09)	7.8 (2.12)
Change from Baseline to Day 3-4	-3.9 (2.46)	-3.8 (2.43)
Change from Baseline to Day 8	-5.9 (2.53)	-5.8 (2.68)
Change from Baseline to EOT Visit	-6.9 (2.37)	-6.9 (2.53)
Change from Baseline to Final Visit	-7.5 (2.19)	-7.4 (2.40)

8. Other Pre-specified Outcome

Title	Percentage of Participants by Resource Utilization Categories
Description	Resource Utilization Categories included: Any additional visits (including urgent care), Any additional procedures, Any additional tests, Any home visits or nursing care and Any ER Visits. The percentage of participants in each category is reported.
Time Frame	Final Visit (Day 28 +/- 2 days)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	323	322
Any Additional Visits (including Urgent Care)	1.2 0.3%	0.6 0.2%
Any Additional Procedures	1.5 0.4%	1.6 0.5%
Any Additional Tests	1.9 0.5%	2.8 0.8%
Any Home Visits or Home Nursing Care	1.5 0.4%	1.2 0.3%
Any ER Visits	0.3 0.1%	0.9 0.3%

9. Other Pre-specified Outcome

Title	Percentage of Participants by Skin and Soft Tissue Infection-Convenience (SSTI-C) Questionnaire: Overall Satisfaction Response
Description	The SSTI-C Questionnaire is an 11-item self-reported questionnaire that measures subjective experiences of the participant. One of the items assessed was overall satisfaction with treatment. Participants answered the question: "Overall, how satisfied were you with your antibiotic treatment?" using one of the following responses: Extremely satisfied, Moderately satisfied, Not at all satisfied, Slightly satisfied and Very satisfied. The percentage of participants in each category is reported.
Time Frame	EOT (Day 14-15)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants regardless of whether or not they received study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Single-Dose Dalbavancin	Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.	Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
Measure Participants	338	332
Extremely Satisfied	53.6 15.4%	56.9 16.3%
Moderately Satisfied	9.5 2.7%	7.2 2.1%
Not at all Satisfied	0.9 0.3%	0.9 0.3%
Slightly Satisfied	0.3 0.1%	0.9 0.3%
Very Satisfied	35.8 10.3%	33.7 9.7%

Adverse Events

Time Frame	Up to 28 Days
Adverse Event Reporting Description	The number of participants at risk for Serious Adverse Events and Adverse Events was based on the Safety Population that included all participants who received at least 1 dose of study treatment.
Arm/Group Title	Single-Dose Dalbavancin		Two-Dose Dalbavancin
Arm/Group Description	Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg.		Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8.
All Cause Mortality
	Single-Dose Dalbavancin		Two-Dose Dalbavancin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/349 (0.3%)		1/346 (0.3%)
Serious Adverse Events
	Single-Dose Dalbavancin		Two-Dose Dalbavancin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/349 (2%)		5/346 (1.4%)
Eye disorders
Vitreous haemorrhage	1/349 (0.3%)		0/346 (0%)
Infections and infestations
Clostridium difficile colitis	0/349 (0%)		1/346 (0.3%)
Necrotising fasciitis	0/349 (0%)		1/346 (0.3%)
Pneumonia	1/349 (0.3%)		0/346 (0%)
Sepsis	1/349 (0.3%)		0/346 (0%)
Skin bacterial infection	2/349 (0.6%)		0/346 (0%)
Injury, poisoning and procedural complications
Toxicity to various agents	1/349 (0.3%)		0/346 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/349 (0.3%)		0/346 (0%)
Renal and urinary disorders
Renal failure acute	0/349 (0%)		1/346 (0.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/349 (0%)		1/346 (0.3%)
Skin and subcutaneous tissue disorders
Urticaria	0/349 (0%)		1/346 (0.3%)
Vascular disorders
Deep vein thrombosis	1/349 (0.3%)		0/346 (0%)
Peripheral ischaemia	1/349 (0.3%)		0/346 (0%)
Phlebitis	1/349 (0.3%)		0/346 (0%)
Other (Not Including Serious) Adverse Events
	Single-Dose Dalbavancin		Two-Dose Dalbavancin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/349 (0%)		0/346 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

PI agrees that the first results publication shall be made in conjunction with a joint multi-center publication. If the multi-center publication is not submitted within 18 months after conclusion of the study at all sites, or if the sponsor confirms not to publish the results, the PI may publish the results from the institution subject to terms of the clinical trial agreement. The publication must be sent to Sponsor at least 60 days before the intended submission date for reference and comment.