Trial Outcomes & Findings for Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia (NCT NCT00695903)

NCT ID: NCT00695903

Last Updated: 2018-12-24

Results Overview

Number of participants with treatment-emergent CPK elevations ≥5 x upper limit of normal (≥1,000 U/L) by the EOT visit.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days)

Results posted on

2018-12-24

Participant Flow

Participant milestones

Participant milestones
Measure	Daptomycin 10 mg/kg Daptomycin 10 mg/kg Intravenously (IV) every 24 hours	Vancomycin High-dose Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Had End of Therapy (EOT) Assessment STARTED	19	19
Had End of Therapy (EOT) Assessment Met Continuation Criteria	9	6
Had End of Therapy (EOT) Assessment COMPLETED	7	4
Had End of Therapy (EOT) Assessment NOT COMPLETED	12	15
Had Test of Cure (TOC) Assessment STARTED	7	4
Had Test of Cure (TOC) Assessment COMPLETED	5	3
Had Test of Cure (TOC) Assessment NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Daptomycin 10 mg/kg Daptomycin 10 mg/kg Intravenously (IV) every 24 hours	Vancomycin High-dose Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Had End of Therapy (EOT) Assessment Randomized not treated	0	2
Had End of Therapy (EOT) Assessment No confirmed MRSA	9	9
Had End of Therapy (EOT) Assessment Adverse Event	1	0
Had End of Therapy (EOT) Assessment Withdrawal by Subject	1	1
Had End of Therapy (EOT) Assessment Physician Decision	0	1
Had End of Therapy (EOT) Assessment Protocol Violation	1	2
Had Test of Cure (TOC) Assessment Lack of Efficacy	1	0
Had Test of Cure (TOC) Assessment Lost to Follow-up	1	0
Had Test of Cure (TOC) Assessment Adverse Event	0	1

Baseline Characteristics

Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daptomycin 10 mg/kg n=19 Participants Daptomycin 10 mg/kg Intravenously (IV) every 24 hours	Vancomycin High-dose n=17 Participants Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days)

Population: All subjects who received at least one dose of study medication (Safety Population). Two patients in the high-dose vancomycin arm were randomized but not treated and therefore not included in the safety population.

Number of participants with treatment-emergent CPK elevations ≥5 x upper limit of normal (≥1,000 U/L) by the EOT visit.

Outcome measures

Outcome measures
Measure	Daptomycin 10 mg/kg n=19 Participants Daptomycin 10 mg/kg Intravenously (IV) every 24 hours	Vancomycin High-dose n=17 Participants Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations	2 Participants Interval 2.9 to 31.4	0 Participants

PRIMARY outcome

Timeframe: On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days)

Number of participants with treatment-emergent serum creatinine increases ≥0.5 mg/dL (for patients with a baseline value ≤3.0 mg/dL) or ≥1.0 mg/dL (for patients with a baseline value \>3.0 mg/dL) by the EOT visit.

Outcome measures

Outcome measures
Measure	Daptomycin 10 mg/kg n=19 Participants Daptomycin 10 mg/kg Intravenously (IV) every 24 hours	Vancomycin High-dose n=17 Participants Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Number of Participants With Elevated Serum Creatinine	0 participants	4 participants Interval 9.6 to 47.3

SECONDARY outcome

Timeframe: End of Therapy (median day 12 and 6.5 in daptomycin and vancomycin modified intent-to treat population, respectively)

Population: Patients who met the continuation criteria (modified intent-to-treat) and had a EOT assessment of clinical outcome.

Investigator's assessment of treatment cure. Treatment Cure includes successful outcomes of both clinical and microbiological assessments. Clinical cure is defined by clinical improvement of symptoms and signs associated with the underlying infection such that no further anti-infective therapy is required. Microbiological Success is defined by the eradication or presumed eradication of baseline infecting methicillin-resistant S. aureus pathogen and no superinfecting pathogen(s) (Gram-positive) or metastatic methicillin-resistant S. aureus pathogens were isolated post therapy.

Outcome measures

Outcome measures
Measure	Daptomycin 10 mg/kg n=7 Participants Daptomycin 10 mg/kg Intravenously (IV) every 24 hours	Vancomycin High-dose n=4 Participants Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Number of Participants With Treatment Cure at End of Therapy (EOT) Visit	6 participants Interval 48.7 to 97.4	3 participants Interval 30.1 to 95.4

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (35 to 49 days post-therapy, approximately week 8)

Population: Subset of modified intent-to-treat population who completed TOC/Safety visit

Investigator's assessment of clinical response. Treatment Cure includes successful outcomes of both clinical and microbiological assessments. Clinical cure is defined by clinical improvement of symptoms and signs associated with the underlying infection such that no further anti-infective therapy is required. Microbiological Success is defined by the eradication or presumed eradication of baseline infecting methicillin-resistant S. aureus pathogen and no superinfecting pathogen(s) (Gram-positive) or metastatic methicillin-resistant S. aureus pathogens were isolated post therapy.

Outcome measures

Outcome measures
Measure	Daptomycin 10 mg/kg n=5 Participants Daptomycin 10 mg/kg Intravenously (IV) every 24 hours	Vancomycin High-dose n=3 Participants Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Number of Participants With Treatment Cure at Test of Cure (TOC)/Safety Visit	5 participants Interval 56.6 to 100.0	3 participants Interval 43.9 to 100.0

Adverse Events

Daptomycin

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Vancomycin

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Daptomycin n=19 participants at risk Daptomycin 10 mg/kg i.v.q24hr	Vancomycin n=17 participants at risk Vancomycin 15 mg/kg i.v., dosed to maintain trough serum concentrations of 15 to 20 ug/mL
Cardiac disorders Atrioventricular block complete	5.3% 1/19 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Congenital, familial and genetic disorders Atrial septal defect	5.3% 1/19 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Gastrointestinal disorders Abdominal pain	5.3% 1/19 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Gastrointestinal disorders Diarrhoea	10.5% 2/19 • Number of events 2 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Gastrointestinal disorders Nausea	5.3% 1/19 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Gastrointestinal disorders Pancreatitis acute	5.3% 1/19 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Gastrointestinal disorders Vomiting	5.3% 1/19 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Infections and infestations Endocarditis bacterial	0.00% 0/19 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	5.9% 1/17 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Infections and infestations Osteomyelitis	0.00% 0/19 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	5.9% 1/17 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Renal and urinary disorders Renal failure	0.00% 0/19 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	5.9% 1/17 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Renal and urinary disorders Renal failure acute	0.00% 0/19 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	5.9% 1/17 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.3% 1/19 • Number of events 1 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.	0.00% 0/17 • Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy). On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.

Other adverse events

Additional Information

Medical Director

Cubist Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first publication is initiated by Cubist. If first publication not published within 1 year of study conclusion or termination, Investigator has right to publish and disclose the data. Prior to any submission for publication, presentation, or communication of results or information arising from the study, Investigator shall provide Cubist at least 90 days for review and comment upon the manuscript or other material for such publication or presentation.
Publication restrictions are in place

Restriction type: OTHER