Study of Debio 1450 for Bacterial Skin Infections

• Sponsor: Debiopharm International SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02426918
• Collaborator: (none)
• Enrollment: 330
• Locations: 22
• Arms: 3
• Duration (Months): 16.1
• Patients Per Site: 15
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of 2 different doses of intravenous and oral Debio 1450 compared with intravenous vancomycin and oral linezolid in the treatment of patients with staphylococcal ABSSSI.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Infections	Drug: Debio 1450 IV; Drug: Debio 1450 Oral; Drug: Linezolid; Drug: Debio 1450 Oral Placebo; Drug: Linezolid Placebo; Drug: Vancomycin IV	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 330 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Multicenter Study of Safety, Tolerability, and Efficacy of Debio 1450 vs Vancomycin (IV)/Linezolid (Oral) in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) Due to Staphylococcus Sensitive or Resistant to Methicillin
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Debio 1450 320/480 mg After 2 doses of Debio 1450 IV (intravenous) therapy, the Debio 1450 320/480 mg daily dose group receives 240 mg Debio 1450 Oral + Linezolid Placebo twice daily (BID).	Drug: Debio 1450 IV; Intravenous (IV) form of Debio 1450 will be supplied in vials containing 50 mg of active pharmaceutical ingredient (API). Intravenous infusions of Debio 1450 (160 mg and 80 mg) will be administered over a 2-hour period BID every 12 hours within a 2-hour window (12 ± 2 hours).; Drug: Debio 1450 Oral; Oral forms of Debio 1450 will be provided as white, opaque, hard gelatin capsules containing 50 mg drug substance (equivalent to 40 mg of Debio 1450).; Drug: Linezolid Placebo; Linezolid placebo will be supplied as film-coated compressed tablets.
Experimental: Debio 1450 160/240 mg After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group receives 120 mg Debio 1450 Oral + Debio 1450 Oral Placebo + Linezolid Placebo BID.	Drug: Debio 1450 IV; Intravenous (IV) form of Debio 1450 will be supplied in vials containing 50 mg of active pharmaceutical ingredient (API). Intravenous infusions of Debio 1450 (160 mg and 80 mg) will be administered over a 2-hour period BID every 12 hours within a 2-hour window (12 ± 2 hours).; Drug: Debio 1450 Oral; Oral forms of Debio 1450 will be provided as white, opaque, hard gelatin capsules containing 50 mg drug substance (equivalent to 40 mg of Debio 1450).; Drug: Debio 1450 Oral Placebo; Debio 1450 placebo will be supplied as white, opaque, hard gelatin capsules.; Drug: Linezolid Placebo; Linezolid placebo will be supplied as film-coated compressed tablets.
Placebo Comparator: Placebo After 2 doses of Vancomycin IV, the Placebo comparator group receives Debio 1450 Oral Placebo + Linezolid 600 mg BID.	Drug: Linezolid; Linezolid for oral administration will be provided as 600-mg film-coated compressed tablets.; Drug: Debio 1450 Oral Placebo; Debio 1450 placebo will be supplied as white, opaque, hard gelatin capsules.; Drug: Vancomycin IV; Vancomycin will be administered BID every 12 ± 2 hours at doses of 1 g or 15 mg/kg as specified in local protocols, with the infusion rate adjusted to 2 hours.

Outcome Measures

Primary Outcome Measures

1. Early Clinical Response Rate (ECRR): Percentage of Responders to Treatment at 48 to 72 Hours From Randomization as Assessed by the Investigator [At 48 to 72 hours from randomization (Day 4)]

   ECRR was defined as the percentage of responders to treatment at 48 to 72 hours from randomization. Responders were the participants who showed greater than or equal to (≥) 20% reduction in area of the primary lesion involving erythema, edema, or induration of the primary ABSSSI lesion (as assessed by the ruler method) at 48 to 72 hours compared to baseline.

Secondary Outcome Measures

1. Clinical Success Rate: Percentage of Participants Assessed by the Investigator as Responders at 48 to 72 Hours From Randomization, at End of Treatment (EOT) and Short-term Follow-up (STFU) [48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19)]

   The Investigator Assessment of Clinical Outcome (IACO) of treatment was assessed for each participant as success or failure at 48 to 72 hours after randomization at EOT and STFU visits. Clinical success was resolution or near resolution of most disease-specific signs and symptoms and no new signs, symptoms, or complications attributable to ABSSSI such that no further antibiotic therapy is required for treatment of original site of infection. Clinical failure was requirement for additional antibiotic therapy for treatment of the original site of infection or incision and drainage of ABSSSI site that was not both anticipated and completed within a 48- to 72-hour window following randomization, or unplanned major surgical intervention required due to failure of study medication or development of osteomyelitis after baseline. Participants who met both success criteria and none of failure criteria were considered as a clinical success for IACO.

2. Clinical Success Rate: Percentage of Participants Assessed by the Sponsor as Responders After 7 to 10 Days of Treatment at EOT and STFU [EOT (Day 12) and STFU (Day 19)]

   The Sponsor's Assessment of Clinical Outcome was obtained at EOT and STFU visits based on IACO and additional criteria. Sponsor assessed participants as clinical failure if they required non-study or rescue antibiotics due to lack of efficacy after at least 48 hours from randomization or experienced drug-related serious adverse events (SAEs) or discontinuation of study medication for drug-related AEs or required antibiotic therapy for longer than 10 days or had the need for unplanned surgical intervention >48 hours after randomization. As per IACO, clinical success was resolution or near resolution of most disease-specific signs and symptoms and no new signs, symptoms or complications. Clinical failure was requirement for additional antibiotic therapy or incision and drainage of ABSSSI site or unplanned major surgical intervention or development of osteomyelitis.

3. Percentage of Participants With a Composite Assessment of Clinical Outcome (CACO) of Success [48 to 72 hours after randomization (Day 4) and STFU (Day 19)]

   CACO of treatment was determined as a combined outcome of early response to treatment (at 48 to 72 hours from randomization) and IACO at the STFU visit. Participants had a CACO of success if they met both of the following criteria: An early response to treatment (at 48 to 72 hours from randomization) (ECR = responder) and a clinical outcome of success at the STFU visit (7 to 14 days after EOT) based on IACO (IACO = success).

4. Percentage of Participants Who Showed Microbiological Evidence of Cure 48 to 72 Hours From Randomization, EOT, and STFU [48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19)]

   The microbiological outcome was assessed by the sponsor at 48 to 72 hours from randomization, EOT and STFU. It was based on blood and skin lesion identification results from baseline samples and skin lesion identification results from baseline samples and skin lesion identification results from follow-up samples as well as on, molecular typing results, and the IACO. Microbiological eradication rate was defined as proportion of participants with 'Documented Eradication' (absence of baseline pathogen(s) in follow-up cultures of the original site of infection.) or 'Presumed Eradication' (no material available for culture and an IACO of 'Success') in relation to the total number of participants in the respective treatment group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has clinically documented infection of the skin or skin structure suspected or documented to be caused by a staphylococcal pathogen

• Meets other protocol-specified criteria for qualification and contraception

• Is willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related to food, drink and medications

• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

1. the safety or well-being of the participant or study staff;

2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);

3. the analysis of results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dream Team Clinical Research, LLC	Anaheim	California	United States	91776
2	Physician Alliance Research Center	Anaheim	California	United States	92804
3	Southbay Pharma Research	Buena Park	California	United States	90620
4	eStudySite - Chula Vista	Chula Vista	California	United States	91911
5	eStudySite - La Mesa	La Mesa	California	United States	91942
6	Long Beach Clinical Trials LLC	Long Beach	California	United States	90806
7	Alliance Research	Long Beach	California	United States	90813
8	Central Valley Research, LLC	Modesto	California	United States	95350
9	eStudySite - Oceanside	Oceanside	California	United States	92056
10	Olive View - UCLA Medical Center	Sylmar	California	United States	91342
11	Shands Burn Center at the University of Florida	Gainesville	Florida	United States	32610
12	Central Florida Internists	Orlando	Florida	United States	32811
13	Triple O Research Institute	West Palm Beach	Florida	United States	33401
14	Columbus Regional Research	Columbus	Georgia	United States	31904
15	Beaumont Infectious Disease Services	Royal Oak	Michigan	United States	48073
16	Mercury Street Medical Group PLLC	Butte	Montana	United States	59701
17	eStudySite - Las Vegas	Las Vegas	Nevada	United States	89109
18	South Jersey Infectious Disease	Somers Point	New Jersey	United States	08244
19	Holy Name Medical Center	Teaneck	New Jersey	United States	07666
20	ID Clinical Research, Ltd.	Toledo	Ohio	United States	43608
21	East Montgomery County Clinic	Houston	Texas	United States	77070
22	Tidwell Medical Center	Splendora	Texas	United States	77372

Sponsors and Collaborators

• Debiopharm International SA

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Debiopharm International SA
• ClinicalTrials.gov Identifier: NCT02426918
• Other Study ID Numbers: Debio 1450-ABSSSI-201; 218187
• First Posted: Apr 27, 2015
• Last Update Posted: Nov 13, 2019
• Last Verified: Oct 1, 2019

• Additional relevant MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Vancomycin; Linezolid

Study Results

Participant Flow

Recruitment Details	Participants took part in the study in the United States, from 14 May 2015 to 12 September 2016. Of the 505 participants screened, 175 discontinued from the study prior to randomization and 330 were randomized.
Pre-assignment Detail	Participants with acute bacterial skin and skin structure infections (ABSSSI) due to Staphylococcus sensitive or resistant to Methicillin were randomized to one of the three treatment arms in a 1:1:1 ratio.

Arm/Group Title	Debio 1450 80 mg (Milligrams)/120 mg BID	Debio 1450 160 mg/240 mg BID	Vancomycin/Linezolid BID
Arm/Group Description	Debio 1450 80 mg was administered intravenously twice daily (BID). After 2 doses of Debio 1450 intravenous (IV) therapy, Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.	Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.	Vancomycin was administered intravenously BID at doses of 1 gram (g) or 15 milligrams per kilogram (mg/kg). After 2 doses of Vancomycin IV, Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.
Period Title: Overall Study
STARTED	110	109	111
Safety Population	110	107	107
COMPLETED	93	90	97
NOT COMPLETED	17	19	14

Baseline Characteristics

Arm/Group Title	Debio 1450 80 mg/120 mg BID	Debio 1450 160 mg/240 mg BID	Vancomycin/Linezolid BID	Total
Arm/Group Description	Debio 1450 80 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.	Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.	Vancomycin was administered intravenously BID at doses of 1 g or 15 mg/kg. After 2 doses of Vancomycin IV, the Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.	Total of all reporting groups
Overall Participants	110	109	111	330
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.9 (11.71)	42.8 (11.72)	44.8 (10.57)	43.8 (11.34)
Sex: Female, Male (Count of Participants)
Female	36 32.7%	35 32.1%	32 28.8%	103 31.2%
Male	74 67.3%	74 67.9%	79 71.2%	227 68.8%

Outcome Measures

1. Primary Outcome

Title	Early Clinical Response Rate (ECRR): Percentage of Responders to Treatment at 48 to 72 Hours From Randomization as Assessed by the Investigator
Description	ECRR was defined as the percentage of responders to treatment at 48 to 72 hours from randomization. Responders were the participants who showed greater than or equal to (≥) 20% reduction in area of the primary lesion involving erythema, edema, or induration of the primary ABSSSI lesion (as assessed by the ruler method) at 48 to 72 hours compared to baseline.
Time Frame	At 48 to 72 hours from randomization (Day 4)

Outcome Measure Data

Analysis Population Description

Microbiological Intent-to-Treat (mITT) population included all randomized participants who were culture positive for any staphylococcal species considered pathogenic and received at least one dose of study medication.

Arm/Group Title	Debio 1450 80 mg/120 mg BID	Debio 1450 160 mg/240 mg BID	Vancomycin/Linezolid BID
Arm/Group Description	Debio 1450 80 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.	Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.	Vancomycin was administered intravenously BID at doses of 1 g or 15 mg/kg. After 2 doses of Vancomycin IV, the Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.
Measure Participants	92	91	101
Number [percentage of participants]	94.6 86%	90.1 82.7%	91.1 82.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Debio 1450 80 mg/120 mg BID, Vancomycin/Linezolid BID
	Comments	Treatment difference estimates and 95% CIs are calculated accounting for the randomization strata infection type [cellulitis, noncellulitis] according to a Mantel-Haenszel type risk difference estimator.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority for the low dose was confirmed if the upper bound of the CI was < 15% and if non-inferiority was confirmed for the high dose.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -11.42 to 3.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Debio 1450 160 mg/240 mg BID, Vancomycin/Linezolid BID
	Comments	Treatment difference estimates and 95% CIs are calculated accounting for the randomization strata infection type [cellulitis, noncellulitis] according to a Mantel-Haenszel type risk difference estimator.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority for the high dose was confirmed if the upper bound of the CI was < 15%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -8.32 to 8.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Clinical Success Rate: Percentage of Participants Assessed by the Investigator as Responders at 48 to 72 Hours From Randomization, at End of Treatment (EOT) and Short-term Follow-up (STFU)
Description	The Investigator Assessment of Clinical Outcome (IACO) of treatment was assessed for each participant as success or failure at 48 to 72 hours after randomization at EOT and STFU visits. Clinical success was resolution or near resolution of most disease-specific signs and symptoms and no new signs, symptoms, or complications attributable to ABSSSI such that no further antibiotic therapy is required for treatment of original site of infection. Clinical failure was requirement for additional antibiotic therapy for treatment of the original site of infection or incision and drainage of ABSSSI site that was not both anticipated and completed within a 48- to 72-hour window following randomization, or unplanned major surgical intervention required due to failure of study medication or development of osteomyelitis after baseline. Participants who met both success criteria and none of failure criteria were considered as a clinical success for IACO.
Time Frame	48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants who were culture positive for any staphylococcal species considered pathogenic and received at least one dose of study medication.

Arm/Group Title	Debio 1450 80 mg/120 mg BID	Debio 1450 160 mg/240 mg BID	Vancomycin/Linezolid BID
Arm/Group Description	Debio 1450 80 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.	Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.	Vancomycin was administered intravenously BID at doses of 1 g or 15 mg/kg. After 2 doses of Vancomycin IV, the Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.
Measure Participants	92	91	101
48 to 72 hours after randomization	83.7 76.1%	81.3 74.6%	86.1 77.6%
EOT	92.4 84%	87.9 80.6%	92.1 83%
STFU	84.8 77.1%	83.5 76.6%	92.1 83%

3. Secondary Outcome

Title	Clinical Success Rate: Percentage of Participants Assessed by the Sponsor as Responders After 7 to 10 Days of Treatment at EOT and STFU
Description	The Sponsor's Assessment of Clinical Outcome was obtained at EOT and STFU visits based on IACO and additional criteria. Sponsor assessed participants as clinical failure if they required non-study or rescue antibiotics due to lack of efficacy after at least 48 hours from randomization or experienced drug-related serious adverse events (SAEs) or discontinuation of study medication for drug-related AEs or required antibiotic therapy for longer than 10 days or had the need for unplanned surgical intervention >48 hours after randomization. As per IACO, clinical success was resolution or near resolution of most disease-specific signs and symptoms and no new signs, symptoms or complications. Clinical failure was requirement for additional antibiotic therapy or incision and drainage of ABSSSI site or unplanned major surgical intervention or development of osteomyelitis.
Time Frame	EOT (Day 12) and STFU (Day 19)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants who were culture positive for any staphylococcal species considered pathogenic and received at least one dose of study medication.

Arm/Group Title	Debio 1450 80 mg/120 mg BID	Debio 1450 160 mg/240 mg BID	Vancomycin/Linezolid BID
Arm/Group Description	Debio 1450 80 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.	Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.	Vancomycin was administered intravenously BID at doses of 1 g or 15 mg/kg. After 2 doses of Vancomycin IV, the Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.
Measure Participants	92	91	101
EOT	89.1 81%	86.8 79.6%	90.1 81.2%
STFU	81.5 74.1%	81.3 74.6%	90.1 81.2%

4. Secondary Outcome

Title	Percentage of Participants With a Composite Assessment of Clinical Outcome (CACO) of Success
Description	CACO of treatment was determined as a combined outcome of early response to treatment (at 48 to 72 hours from randomization) and IACO at the STFU visit. Participants had a CACO of success if they met both of the following criteria: An early response to treatment (at 48 to 72 hours from randomization) (ECR = responder) and a clinical outcome of success at the STFU visit (7 to 14 days after EOT) based on IACO (IACO = success).
Time Frame	48 to 72 hours after randomization (Day 4) and STFU (Day 19)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants who were culture positive for any staphylococcal species considered pathogenic and received at least one dose of study medication.

Arm/Group Title	Debio 1450 80 mg/120 mg BID	Debio 1450 160 mg/240 mg BID	Vancomycin/Linezolid BID
Arm/Group Description	Debio 1450 80 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.	Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.	Vancomycin was administered intravenously BID at doses of 1 g or 15 mg/kg. After 2 doses of Vancomycin IV, the Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.
Measure Participants	92	91	101
Number [percentage of participants]	83.7 76.1%	81.3 74.6%	88.1 79.4%

5. Secondary Outcome

Title	Percentage of Participants Who Showed Microbiological Evidence of Cure 48 to 72 Hours From Randomization, EOT, and STFU
Description	The microbiological outcome was assessed by the sponsor at 48 to 72 hours from randomization, EOT and STFU. It was based on blood and skin lesion identification results from baseline samples and skin lesion identification results from baseline samples and skin lesion identification results from follow-up samples as well as on, molecular typing results, and the IACO. Microbiological eradication rate was defined as proportion of participants with 'Documented Eradication' (absence of baseline pathogen(s) in follow-up cultures of the original site of infection.) or 'Presumed Eradication' (no material available for culture and an IACO of 'Success') in relation to the total number of participants in the respective treatment group.
Time Frame	48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19)

Outcome Measure Data

Analysis Population Description

mITT population included all randomized participants who were culture positive for any staphylococcal species considered pathogenic and received at least one dose of study medication.

Arm/Group Title	Debio 1450 80 mg/120 mg BID	Debio 1450 160 mg/240 mg BID	Vancomycin/Linezolid BID
Arm/Group Description	Debio 1450 80 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.	Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.	Vancomycin was administered intravenously BID at doses of 1 g or 15 mg/kg. After 2 doses of Vancomycin IV, the Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.
Measure Participants	92	91	101
48 to 72 hours after randomization	72.8 66.2%	69.2 63.5%	75.2 67.7%
EOT	92.4 84%	86.8 79.6%	91.1 82.1%
STFU	84.8 77.1%	83.5 76.6%	91.1 82.1%

Adverse Events

Time Frame	21 days after EOT (Day 33)
Adverse Event Reporting Description	Safety population included all participants who received at least one dose of study medication.
Arm/Group Title	Debio 1450 80 mg/120 mg BID		Debio 1450 160 mg/240 mg BID		Vancomycin/Linezolid BID
Arm/Group Description	Debio 1450 80 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 80 mg/120 mg daily dose group received 120 mg Debio 1450 Oral + 3 dose of Debio 1450 Placebo + Linezolid matching-Placebo BID.		Debio 1450 160 mg was administered intravenously BID. After 2 doses of Debio 1450 IV therapy, the Debio 1450 160/240 mg daily dose group received 240 mg Debio 1450 Oral + Linezolid matching-Placebo BID.		Vancomycin was administered intravenously BID at doses of 1 g or 15 mg/kg. After 2 doses of Vancomycin IV, the Placebo comparator group received Debio 1450 matching oral placebo + Linezolid 600 mg BID.
All Cause Mortality
	Debio 1450 80 mg/120 mg BID		Debio 1450 160 mg/240 mg BID		Vancomycin/Linezolid BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Debio 1450 80 mg/120 mg BID		Debio 1450 160 mg/240 mg BID		Vancomycin/Linezolid BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/110 (1.8%)		1/107 (0.9%)		1/107 (0.9%)
Infections and infestations
Cellulitis	0/110 (0%)		0/107 (0%)		1/107 (0.9%)
Skin infection	2/110 (1.8%)		0/107 (0%)		0/107 (0%)
Injury, poisoning and procedural complications
Overdose	0/110 (0%)		1/107 (0.9%)		0/107 (0%)
Other (Not Including Serious) Adverse Events
	Debio 1450 80 mg/120 mg BID		Debio 1450 160 mg/240 mg BID		Vancomycin/Linezolid BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/110 (16.4%)		29/107 (27.1%)		20/107 (18.7%)
Gastrointestinal disorders
Diarrhoea	3/110 (2.7%)		3/107 (2.8%)		6/107 (5.6%)
Nausea	7/110 (6.4%)		9/107 (8.4%)		7/107 (6.5%)
Vomiting	1/110 (0.9%)		6/107 (5.6%)		2/107 (1.9%)
Infections and infestations
Abscess	3/110 (2.7%)		6/107 (5.6%)		0/107 (0%)
Nervous system disorders
Headache	10/110 (9.1%)		18/107 (16.8%)		9/107 (8.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Any publication or scientific communication related to this study can only take place once the agreement between the Sponsor and the Investigator has been reached.