Trial Outcomes & Findings for Study of Debio 1450 for Bacterial Skin Infections (NCT NCT02426918)

NCT ID: NCT02426918

Last Updated: 2019-11-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 330 participants
• Primary outcome timeframe: At 48 to 72 hours from randomization (Day 4)
• Results posted on: 2019-11-13

Participant Flow

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.

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.

Participant milestones

Measure	Debio 1450 80 mg (Milligrams)/120 mg BID 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/240 mg 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/Linezolid 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.
Overall Study STARTED	110	109	111
Overall Study Safety Population	110	107	107
Overall Study COMPLETED	93	90	97
Overall Study NOT COMPLETED	17	19	14

Reasons for withdrawal

Measure	Debio 1450 80 mg (Milligrams)/120 mg BID 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/240 mg 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/Linezolid 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.
Overall Study Adverse Event	2	2	0
Overall Study Physician Decision	1	1	1
Overall Study Withdrawal by Subject	5	5	4
Overall Study Other	9	11	9

Baseline Characteristics

Study of Debio 1450 for Bacterial Skin Infections

Baseline characteristics by cohort

Measure	Debio 1450 80 mg/120 mg BID n=110 Participants 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/240 mg BID n=109 Participants 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/Linezolid BID n=111 Participants 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 n=330 Participants Total of all reporting groups
Age, Continuous	43.9 years STANDARD_DEVIATION 11.71 • n=5 Participants	42.8 years STANDARD_DEVIATION 11.72 • n=7 Participants	44.8 years STANDARD_DEVIATION 10.57 • n=5 Participants	43.8 years STANDARD_DEVIATION 11.34 • n=4 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	35 Participants n=7 Participants	32 Participants n=5 Participants	103 Participants n=4 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	74 Participants n=7 Participants	79 Participants n=5 Participants	227 Participants n=4 Participants

PRIMARY outcome

Timeframe: At 48 to 72 hours from randomization (Day 4)

Population: 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.

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.

Outcome measures

Measure	Debio 1450 80 mg/120 mg BID n=92 Participants 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/240 mg BID n=91 Participants 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/Linezolid BID n=101 Participants 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.
Early Clinical Response Rate (ECRR): Percentage of Responders to Treatment at 48 to 72 Hours From Randomization as Assessed by the Investigator	94.6 percentage of participants	90.1 percentage of participants	91.1 percentage of participants

SECONDARY outcome

Timeframe: 48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19)

Population: 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.

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.

Outcome measures

Measure	Debio 1450 80 mg/120 mg BID n=92 Participants 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/240 mg BID n=91 Participants 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/Linezolid BID n=101 Participants 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.
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) STFU	84.8 percentage of participants	83.5 percentage of participants	92.1 percentage of participants
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	83.7 percentage of participants	81.3 percentage of participants	86.1 percentage of participants
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) EOT	92.4 percentage of participants	87.9 percentage of participants	92.1 percentage of participants

SECONDARY outcome

Timeframe: EOT (Day 12) and STFU (Day 19)

Population: 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.

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.

Outcome measures

Measure	Debio 1450 80 mg/120 mg BID n=92 Participants 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/240 mg BID n=91 Participants 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/Linezolid BID n=101 Participants 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.
Clinical Success Rate: Percentage of Participants Assessed by the Sponsor as Responders After 7 to 10 Days of Treatment at EOT and STFU EOT	89.1 percentage of participants	86.8 percentage of participants	90.1 percentage of participants
Clinical Success Rate: Percentage of Participants Assessed by the Sponsor as Responders After 7 to 10 Days of Treatment at EOT and STFU STFU	81.5 percentage of participants	81.3 percentage of participants	90.1 percentage of participants

SECONDARY outcome

Timeframe: 48 to 72 hours after randomization (Day 4) and STFU (Day 19)

Population: 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.

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).

Outcome measures

Measure	Debio 1450 80 mg/120 mg BID n=92 Participants 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/240 mg BID n=91 Participants 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/Linezolid BID n=101 Participants 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.
Percentage of Participants With a Composite Assessment of Clinical Outcome (CACO) of Success	83.7 percentage of participants	81.3 percentage of participants	88.1 percentage of participants

SECONDARY outcome

Timeframe: 48 to 72 hours after randomization (Day 4), EOT (Day 12) and STFU (Day 19)

Population: 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.

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.

Outcome measures

Measure	Debio 1450 80 mg/120 mg BID n=92 Participants 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/240 mg BID n=91 Participants 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/Linezolid BID n=101 Participants 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.
Percentage of Participants Who Showed Microbiological Evidence of Cure 48 to 72 Hours From Randomization, EOT, and STFU 48 to 72 hours after randomization	72.8 percentage of participants	69.2 percentage of participants	75.2 percentage of participants
Percentage of Participants Who Showed Microbiological Evidence of Cure 48 to 72 Hours From Randomization, EOT, and STFU EOT	92.4 percentage of participants	86.8 percentage of participants	91.1 percentage of participants
Percentage of Participants Who Showed Microbiological Evidence of Cure 48 to 72 Hours From Randomization, EOT, and STFU STFU	84.8 percentage of participants	83.5 percentage of participants	91.1 percentage of participants

Adverse Events

Debio 1450 80 mg/120 mg BID

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Debio 1450 160 mg/240 mg BID

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Vancomycin/Linezolid BID

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Debio 1450 80 mg/120 mg BID n=110 participants at risk 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/240 mg BID n=107 participants at risk 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/Linezolid BID n=107 participants at risk 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.
Infections and infestations Cellulitis	0.00% 0/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	0.00% 0/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	0.93% 1/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.
Infections and infestations Skin infection	1.8% 2/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	0.00% 0/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	0.00% 0/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Overdose	0.00% 0/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	0.93% 1/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	0.00% 0/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.

Other adverse events

Measure	Debio 1450 80 mg/120 mg BID n=110 participants at risk 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/240 mg BID n=107 participants at risk 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/Linezolid BID n=107 participants at risk 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.
Gastrointestinal disorders Diarrhoea	2.7% 3/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	2.8% 3/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	5.6% 6/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.
Gastrointestinal disorders Nausea	6.4% 7/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	8.4% 9/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	6.5% 7/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	0.91% 1/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	5.6% 6/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	1.9% 2/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.
Infections and infestations Abscess	2.7% 3/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	5.6% 6/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	0.00% 0/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.
Nervous system disorders Headache	9.1% 10/110 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	16.8% 18/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.	8.4% 9/107 • 21 days after EOT (Day 33) Safety population included all participants who received at least one dose of study medication.

Additional Information

Vice President Clinical Research & Development

Debiopharm International S.A.

Phone: 4121 321 01 11

Email: info-international@debiopharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER