Trial Outcomes & Findings for Study of Tedizolid Phosphate in Adolescents With Complicated Skin and Soft Tissue Infection (cSSTI) (MK-1986-012) (NCT NCT02276482)

NCT ID: NCT02276482

Last Updated: 2019-08-07

Results Overview

An adverse event (AE) refers to a treatment-emergent adverse event (TE-AE). A TE-AE is any AE that newly appeared, increased in frequency, or worsened in severity following initiation of study drug.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 120 participants
• Primary outcome timeframe: Up to 40 days (including 30-day follow-up)
• Results posted on: 2019-08-07

Participant Flow

All participants who were enrolled and provided informed consent/ascent were randomized to one of two treatment groups.

Participant milestones

Measure	Tedizolid Phosphate Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Overall Study STARTED	91	29
Overall Study COMPLETED	88	28
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Measure	Tedizolid Phosphate Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Gram-negative infection	1	0
Overall Study Reason not specified	0	1

Baseline Characteristics

Study of Tedizolid Phosphate in Adolescents With Complicated Skin and Soft Tissue Infection (cSSTI) (MK-1986-012)

Baseline characteristics by cohort

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=29 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Total n=120 Participants Total of all reporting groups
Age, Continuous	14.4 Years STANDARD_DEVIATION 1.7 • n=5 Participants	14.4 Years STANDARD_DEVIATION 2.0 • n=7 Participants	14.4 Years STANDARD_DEVIATION 1.7 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	12 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	17 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	86 Participants n=5 Participants	28 Participants n=7 Participants	114 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	80 Participants n=5 Participants	24 Participants n=7 Participants	104 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 40 days (including 30-day follow-up)

Population: All randomized participants who received at least one dose of study drug.

An adverse event (AE) refers to a treatment-emergent adverse event (TE-AE). A TE-AE is any AE that newly appeared, increased in frequency, or worsened in severity following initiation of study drug.

Outcome measures

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=29 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Number of Participants With Adverse Events on Tedizolid Phosphate and Comparator Drugs	13 Participants	3 Participants

SECONDARY outcome

Timeframe: TOC Visit: 18-25 days after first drug infusion

Population: All randomized participants.

Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.

Outcome measures

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=29 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Number of Participants With Investigator's Assessment Indicating Clinical Success at Test of Cure (TOC) Visit (Intent to Treat Analysis Set)	88 Participants	27 Participants

SECONDARY outcome

Timeframe: TOC Visit: 18-25 days after first drug infusion

Population: All randomized participants who received a full dose of study treatment and completed TOC.

Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.

Outcome measures

Measure	Tedizolid Phosphate n=87 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=27 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Number of Participants With Investigator's Assessment Indicating Clinical Success at TOC Visit (Clinically Evaluable-Test of Cure [CE-TOC] Analysis Set)	87 Participants	26 Participants

SECONDARY outcome

Timeframe: 48-72 hr after first drug infusion

Population: All randomized participants.

Early clinical response is defined as ≥20% reduction from baseline lesion area (defined as length multiplied by the width of the erythema, edema, and/or induration [EEI]) at the 48-72 hour (hr) visit.

Outcome measures

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=29 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Number of Participants With Early Clinical Responses Measured by Lesion Reduction	84 Participants	28 Participants

SECONDARY outcome

Timeframe: EOT Visit: up to 13 days after first drug infusion

Population: All randomized participants.

Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.

Outcome measures

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=29 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Number of Participants With Investigator's Assessment Indicating Clinical Success at End of Therapy (EOT) Visit (Intent to Treat Analysis Set)	88 Participants	28 Participants

SECONDARY outcome

Timeframe: EOT Visit: up to 13 days after first drug infusion

Population: All randomized participants received a full dose of study treatment and completed EOT.

Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2) absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.

Outcome measures

Measure	Tedizolid Phosphate n=87 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=27 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Number of Participants With Investigator's Assessment Indicating Clinical Success at EOT Visit (Clinically Evaluable-End of Therapy [CE-EOT] Analysis Set)	87 Participants	27 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and TOC visit (18 to 25 days after infusion)

Population: All randomized participants who received a full dose of study treatment, had a baseline value and a TOC visit value (Days 18 to 25).

Lesion size is the area in cm^2 of erythema, edema or induration. A negative number corresponds to a decrease in lesion size.

Outcome measures

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=29 Participants IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Change From Baseline in Lesion Size Baseline	135.44 cm^2 Standard Deviation 158.66	83.22 cm^2 Standard Deviation 48.55
Change From Baseline in Lesion Size Change at Day 25	-134.27 cm^2 Standard Deviation 161.18	-82.51 cm^2 Standard Deviation 49.94

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 at 5-80 minutes (min) and 4-12 hrs post-infusion or 2 samples collected between 4-12 hrs after oral dose, at least 60 min apart; at 48-72 hrs: within 60 min prior to administration and 4-12 hrs after administration; and anytime between Day 7 and 9

Population: All randomized participants who received a dose of tedizolid phosphate. Pharmacokinetic analysis was not performed with participants receiving antibiotic comparator drug.

The Cmax of tedizolid in plasma after the last dose was estimated based on population pharmacokinetic analysis of observed pharmacokinetic data. Blood samples were collected for pharmacokinetic analysis at specific time points.

Outcome measures

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Peak Plasma Concentration (Cmax) of Tedizolid	3.13 µg/mL Interval 2.89 to 3.38	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 at 5-80 min and 4-12 hrs post-infusion or 2 samples collected between 4-12 hrs after oral dose, at least 60 min apart; at 48-72 hrs: within 60 min prior to administration and 4-12 hrs after administration; and anytime between Day 7 and 9

Population: All randomized participants who received a dose of tedizolid phosphate. Pharmacokinetic analysis was not performed with participants receiving antibiotic comparator drug.

AUC0-24h is a measure of the total tedizolid exposure in the plasma from the dose to 24 hours after last dose. AUC0-24h was estimated based on population pharmacokinetic analysis of observed pharmacokinetic data. Blood samples were collected for pharmacokinetic analysis at specific time points.

Outcome measures

Measure	Tedizolid Phosphate n=91 Participants Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Area Under the Plasma Concentration Versus Time Curve Time 0 to 24 Hours (AUC0-24h) of Tedizolid	28.6 µg*h/mL Interval 26.6 to 30.8	—

Adverse Events

Tedizolid Phosphate

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Antibiotic Comparator Drug

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tedizolid Phosphate n=91 participants at risk Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).	Antibiotic Comparator Drug n=29 participants at risk IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Infections and infestations Pneumonia	1.1% 1/91 • Number of events 1 • Up to 40 days (including 30-day follow-up)	0.00% 0/29 • Up to 40 days (including 30-day follow-up)
Infections and infestations Sepsis	1.1% 1/91 • Number of events 1 • Up to 40 days (including 30-day follow-up)	0.00% 0/29 • Up to 40 days (including 30-day follow-up)
Vascular disorders Venous Thrombosis Limb	1.1% 1/91 • Number of events 1 • Up to 40 days (including 30-day follow-up)	0.00% 0/29 • Up to 40 days (including 30-day follow-up)

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme, Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

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 study agreement between Sponsor and Investigators. Sponsor approval in writing is required for publication of any data subsets.
• Publication restrictions are in place

Restriction type: OTHER