Trial Outcomes & Findings for Phase 2 Study of TR-701 in Patients With Complicated Skin and Skin Structure Infections (NCT NCT00761215)

Last Updated: 2019-11-25

Results Overview

Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

192 participants

Primary outcome timeframe

7 to 14 days after the last dose of study drug

Results posted on

2019-11-25

Participant Flow

Participant milestones

Participant milestones
Measure	TR-701 200 mg Oral TR-701 200 mg once daily for 5 to 7 days	TR-701 300 mg Oral TR-701 300 mg once daily for 5 to 7 days	TR-701 400 mg Oral TR-701 400 mg once daily for 5 to 7 days
Overall Study STARTED	64	64	64
Overall Study COMPLETED	55	60	56
Overall Study NOT COMPLETED	9	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	TR-701 200 mg Oral TR-701 200 mg once daily for 5 to 7 days	TR-701 300 mg Oral TR-701 300 mg once daily for 5 to 7 days	TR-701 400 mg Oral TR-701 400 mg once daily for 5 to 7 days
Overall Study Randomized but didn't receive drug	1	1	2
Overall Study Lost to Follow-up	6	3	6
Overall Study Withdrawal by Subject	1	0	0
Overall Study Bacteremia	1	0	0

Baseline Characteristics

Phase 2 Study of TR-701 in Patients With Complicated Skin and Skin Structure Infections

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TR-701 200 mg n=63 Participants Oral TR-701 200 mg once daily for 5 to 7 days	TR-701 300 mg n=63 Participants Oral TR-701 300 mg once daily for 5 to 7 days	TR-701 400 mg n=62 Participants Oral TR-701 400 mg once daily for 5 to 7 days	Total n=188 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 12.1 • n=93 Participants	36.0 years STANDARD_DEVIATION 12.4 • n=4 Participants	35.8 years STANDARD_DEVIATION 12.0 • n=27 Participants	36.4 years STANDARD_DEVIATION 12.1 • n=483 Participants
Sex: Female, Male Female	20 Participants n=93 Participants	24 Participants n=4 Participants	22 Participants n=27 Participants	66 Participants n=483 Participants
Sex: Female, Male Male	43 Participants n=93 Participants	39 Participants n=4 Participants	40 Participants n=27 Participants	122 Participants n=483 Participants

PRIMARY outcome

Timeframe: 7 to 14 days after the last dose of study drug

Population: The Clinically Evaluable analysis set includes data from all participants who had a diagnosis of cSSSI, received minimal study therapy, completed an assessment, and had no confounding events or factors.

Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required.

Outcome measures

Outcome measures
Measure	TR-701 200 mg n=56 Participants Oral TR-701 200 mg for 5 to 7 days	TR-701 300 mg n=54 Participants Oral TR-701 300 mg for 5 to 7 days	TR-701 400 mg n=54 Participants Oral TR-701 400 mg for 5 to 7 days
Clinical Response Rate at Test of Cure in the Clinically Evaluable Analysis Set	98.2 Percentage of participants Interval 90.4 to 100.0	94.4 Percentage of participants Interval 84.6 to 98.8	94.4 Percentage of participants Interval 84.6 to 98.8

PRIMARY outcome

Timeframe: 7-14 days after last dose of study drug

Population: The clinically modified intent to treat analysis set includes data from all participants who received study drug and had a diagnosis of complicated skin and skin structure infection.

Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required.

Outcome measures

Outcome measures
Measure	TR-701 200 mg n=63 Participants Oral TR-701 200 mg for 5 to 7 days	TR-701 300 mg n=63 Participants Oral TR-701 300 mg for 5 to 7 days	TR-701 400 mg n=62 Participants Oral TR-701 400 mg for 5 to 7 days
Clinical Response Rate at Test of Cure in the Clinical Modified Intent to Treat Analysis Set	88.9 Percentage of participants Interval 78.4 to 95.4	88.9 Percentage of participants Interval 78.4 to 95.4	85.5 Percentage of participants Interval 74.2 to 93.1

SECONDARY outcome

Timeframe: last day of study treatment

Population: The clinical modified intent to treat analysis set includes data from all participants who received study drug and had a diagnosis of complicated skin and skin structure infection

Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required.

Outcome measures

Outcome measures
Measure	TR-701 200 mg n=63 Participants Oral TR-701 200 mg for 5 to 7 days	TR-701 300 mg n=63 Participants Oral TR-701 300 mg for 5 to 7 days	TR-701 400 mg n=62 Participants Oral TR-701 400 mg for 5 to 7 days
Response Rate at End of Therapy	93.7 Percentage of participants Interval 84.5 to 98.2	90.5 Percentage of participants Interval 80.4 to 96.4	91.9 Percentage of participants Interval 82.2 to 97.3

SECONDARY outcome

Timeframe: 7-14 days after last dose of study drug

Population: The microbiologically evaluable analysis set includes all participants who received study drug, had a diagnosis of complicated skin and skin structure infection, completed an assessment, had no confounding events or factors, and had a baseline Gram-positive bacterial pathogen.

Satisfactory microbiological outcomes are eradication and presumed eradication

Outcome measures

Outcome measures
Measure	TR-701 200 mg n=43 Participants Oral TR-701 200 mg for 5 to 7 days	TR-701 300 mg n=44 Participants Oral TR-701 300 mg for 5 to 7 days	TR-701 400 mg n=46 Participants Oral TR-701 400 mg for 5 to 7 days
Microbiological Response Rate at Test of Cure in the Microbiologically Evaluable Analysis Set	100 Percentage of participants Interval 91.8 to 100.0	93.2 Percentage of participants Interval 81.3 to 98.6	100 Percentage of participants Interval 92.3 to 100.0

SECONDARY outcome

Timeframe: 21 to 28 days after the last study drug

Population: The clinical modified intent to treat analysis set includes data from all participants who received study drug and had a diagnosis of complicated skin and skin structure infection. Microbiological samples not available from all participants.

Persistent clinical cure was defined as continuing favorable response.

Outcome measures

Outcome measures
Measure	TR-701 200 mg n=56 Participants Oral TR-701 200 mg for 5 to 7 days	TR-701 300 mg n=56 Participants Oral TR-701 300 mg for 5 to 7 days	TR-701 400 mg n=53 Participants Oral TR-701 400 mg for 5 to 7 days
Clinical Outcome at the Late Follow-up Visit in the Clinical Modified Intent to Treat Analysis Set	96.4 Percentage of Participants	98.2 Percentage of Participants	98.1 Percentage of Participants

SECONDARY outcome

Timeframe: Multiple

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Multiple

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 21-28 days after last study drug

Outcome measures

Outcome measures
Measure	TR-701 200 mg n=56 Participants Oral TR-701 200 mg for 5 to 7 days	TR-701 300 mg n=56 Participants Oral TR-701 300 mg for 5 to 7 days	TR-701 400 mg n=53 Participants Oral TR-701 400 mg for 5 to 7 days
Microbiological Recurrence at Late Follow-up in Clinical Modified Intent to Treat Analysis Set	0 Percentage of participants Interval 0.0 to 6.4	0 Percentage of participants Interval 0.0 to 6.4	0 Percentage of participants Interval 0.0 to 6.7

Adverse Events

TR-701 200 mg

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

TR-701 300 mg

Serious events: 1 serious events

Other events: 44 other events

Deaths: 0 deaths

TR-701 400 mg

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TR-701 200 mg n=63 participants at risk Oral TR-701 200 mg once daily for 5 to 7 days	TR-701 300 mg n=63 participants at risk Oral TR-701 300 mg once daily for 5 to 7 days	TR-701 400 mg n=62 participants at risk Oral TR-701 400 mg once daily for 5 to 7 days
Hepatobiliary disorders Cholecystitis acute	0.00% 0/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	0.00% 0/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Psychiatric disorders Suicidal ideation	0.00% 0/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	0.00% 0/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Infections and infestations Abcess	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	0.00% 0/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Infections and infestations Cellulitis	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	0.00% 0/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	0.00% 0/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).

Other adverse events

Additional Information

Philippe Prokocimer, MD

Cubist Pharmaceuticals, Inc.

Phone: 858-452-0370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor intends to pursue publication of the results of the study in cooperation with a lead Investigator, subject to the terms and conditions of the clinical trial agreement between Sponsor and Investigators. Sponsor approval is required for publication of any data subsets. Final authorship will be determined by contributions to study design, enrollment, data analysis, and/or interpretation of the results.
Publication restrictions are in place

Restriction type: OTHER

Measure	TR-701 200 mg n=63 participants at risk Oral TR-701 200 mg once daily for 5 to 7 days	TR-701 300 mg n=63 participants at risk Oral TR-701 300 mg once daily for 5 to 7 days	TR-701 400 mg n=62 participants at risk Oral TR-701 400 mg once daily for 5 to 7 days
Cardiac disorders Tachycardia	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Gastrointestinal disorders Diarrhea	11.1% 7/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	4.8% 3/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	9.7% 6/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Gastrointestinal disorders Dry mouth	0.00% 0/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Gastrointestinal disorders Nausea	15.9% 10/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	19.0% 12/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	21.0% 13/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Gastrointestinal disorders Vomiting	11.1% 7/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	9.5% 6/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	9.7% 6/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
General disorders Fatigue	4.8% 3/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
General disorders Pain	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Infections and infestations Abscess	7.9% 5/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	12.7% 8/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	11.3% 7/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Infections and infestations Skin infection	6.3% 4/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Investigations Blood pressure increased	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	6.3% 4/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Metabolism and nutrition disorders Decreased appetite	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Nervous system disorders Dizziness	6.3% 4/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	0.00% 0/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Nervous system disorders Headache	7.9% 5/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	15.9% 10/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	9.7% 6/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Psychiatric disorders Insomnia	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	6.3% 4/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	4.8% 3/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Respiratory, thoracic and mediastinal disorders Rhinorrhea	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Skin and subcutaneous tissue disorders Pruritus	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Skin and subcutaneous tissue disorders Rash	1.6% 1/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).
Skin and subcutaneous tissue disorders Skin lesion	6.3% 4/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	3.2% 2/63 • Adverse events were to be collected after informed consent through last visit (up to 36 days).	1.6% 1/62 • Adverse events were to be collected after informed consent through last visit (up to 36 days).