Trial Outcomes & Findings for Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Minocin (Minocycline) for Injection in Healthy Adults (NCT NCT02802631)

Last Updated: 2023-12-15

Results Overview

Safety and tolerability of single and multiple intravenous doses of Minocin (minocycline) for Injection assessed by number of participants with adverse events.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

69 participants

Primary outcome timeframe

Day 1 through Day 17

Results posted on

2023-12-15

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1 100 milligrams (mg) of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3 180 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Day 4 Due to a dosing error, participants received doses of 180 mg instead of 300 mg as planned. The cohort was discontinued on Day 5 after detection of the dosing error and replaced by Cohort 3b.	Cohort 3b 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 4 400 mg of Minocin (minocycline) for Injection on Day 1 then 400 mg every 12 hours on Days 4 to 7 and a single dose on Day 8	Cohort 5 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-milliliter (mL) bags of normal saline (0.9% Sodium Chloride Injection United States Pharmacopeia \[USP\]). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Overall Study STARTED	8	8	6	8	8	8	9	14
Overall Study COMPLETED	6	6	0	7	0	7	4	10
Overall Study NOT COMPLETED	2	2	6	1	8	1	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 100 milligrams (mg) of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3 180 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Day 4 Due to a dosing error, participants received doses of 180 mg instead of 300 mg as planned. The cohort was discontinued on Day 5 after detection of the dosing error and replaced by Cohort 3b.	Cohort 3b 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 4 400 mg of Minocin (minocycline) for Injection on Day 1 then 400 mg every 12 hours on Days 4 to 7 and a single dose on Day 8	Cohort 5 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-milliliter (mL) bags of normal saline (0.9% Sodium Chloride Injection United States Pharmacopeia \[USP\]). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Overall Study Withdrawal by Subject	1	0	0	0	0	0	0	0
Overall Study Physician Decision	1	0	0	0	0	0	1	0
Overall Study Adverse Event	0	2	0	1	6	1	4	0
Overall Study Sponsor Decision	0	0	6	0	2	0	0	4

Baseline Characteristics

Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Minocin (Minocycline) for Injection in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=8 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3 n=6 Participants 180 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Day 4 Due to a dosing error, participants received doses of 180 mg instead of 300 mg as planned. The cohort was discontinued on Day 5 after detection of the dosing error and replaced by Cohort 3b.	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 4 n=8 Participants 400 mg of Minocin (minocycline) for Injection on Day 1 then 400 mg every 12 hours on Days 4 to 7 and a single dose on Day 8	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 n=9 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo n=14 Participants Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.	Total n=69 Participants Total of all reporting groups
Age, Continuous	26.63 years STANDARD_DEVIATION 7.76 • n=5 Participants	31.00 years STANDARD_DEVIATION 7.45 • n=7 Participants	28.83 years STANDARD_DEVIATION 9.75 • n=5 Participants	25.00 years STANDARD_DEVIATION 7.45 • n=4 Participants	29.63 years STANDARD_DEVIATION 8.72 • n=21 Participants	25.75 years STANDARD_DEVIATION 8.76 • n=10 Participants	30.56 years STANDARD_DEVIATION 12.12 • n=115 Participants	27.43 years STANDARD_DEVIATION 8.23 • n=24 Participants	28.06 years STANDARD_DEVIATION 8.65 • n=42 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=10 Participants	4 Participants n=115 Participants	7 Participants n=24 Participants	25 Participants n=42 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	6 Participants n=10 Participants	5 Participants n=115 Participants	7 Participants n=24 Participants	44 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=24 Participants	2 Participants n=42 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	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=24 Participants	4 Participants n=42 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	7 Participants n=21 Participants	6 Participants n=10 Participants	7 Participants n=115 Participants	14 Participants n=24 Participants	63 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Region of Enrollment Netherlands	8 participants n=5 Participants	8 participants n=7 Participants	6 participants n=5 Participants	8 participants n=4 Participants	8 participants n=21 Participants	8 participants n=10 Participants	9 participants n=115 Participants	14 participants n=24 Participants	69 participants n=42 Participants
Body Mass Index	23.3 kilogram/square meter STANDARD_DEVIATION 2.6 • n=5 Participants	23.2 kilogram/square meter STANDARD_DEVIATION 2.7 • n=7 Participants	22.5 kilogram/square meter STANDARD_DEVIATION 3.4 • n=5 Participants	22.5 kilogram/square meter STANDARD_DEVIATION 2.4 • n=4 Participants	22.7 kilogram/square meter STANDARD_DEVIATION 2.9 • n=21 Participants	22.9 kilogram/square meter STANDARD_DEVIATION 2.5 • n=10 Participants	23.4 kilogram/square meter STANDARD_DEVIATION 3.0 • n=115 Participants	22.1 kilogram/square meter STANDARD_DEVIATION 2.8 • n=24 Participants	22.8 kilogram/square meter STANDARD_DEVIATION 2.7 • n=42 Participants
Height	179.3 centimeter STANDARD_DEVIATION 9.8 • n=5 Participants	175.8 centimeter STANDARD_DEVIATION 7.6 • n=7 Participants	181.36 centimeter STANDARD_DEVIATION 11.2 • n=5 Participants	178.1 centimeter STANDARD_DEVIATION 7.1 • n=4 Participants	175.4 centimeter STANDARD_DEVIATION 9.2 • n=21 Participants	178.0 centimeter STANDARD_DEVIATION 6.0 • n=10 Participants	176.4 centimeter STANDARD_DEVIATION 11.0 • n=115 Participants	178.1 centimeter STANDARD_DEVIATION 10.1 • n=24 Participants	177.7 centimeter STANDARD_DEVIATION 8.9 • n=42 Participants
Weight	75.1 kilogram STANDARD_DEVIATION 10.6 • n=5 Participants	71.7 kilogram STANDARD_DEVIATION 9.0 • n=7 Participants	73.4 kilogram STANDARD_DEVIATION 10.1 • n=5 Participants	71.6 kilogram STANDARD_DEVIATION 10.1 • n=4 Participants	69.9 kilogram STANDARD_DEVIATION 11.6 • n=21 Participants	72.6 kilogram STANDARD_DEVIATION 8.0 • n=10 Participants	73.0 kilogram STANDARD_DEVIATION 12.7 • n=115 Participants	70.9 kilogram STANDARD_DEVIATION 14.6 • n=24 Participants	72.1 kilogram STANDARD_DEVIATION 11.0 • n=42 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 17

Population: Safety Population: all enrolled participants who received at least 1 dose of study drug.

Safety and tolerability of single and multiple intravenous doses of Minocin (minocycline) for Injection assessed by number of participants with adverse events.

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=8 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=8 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=6 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 n=9 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo n=14 Participants Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Number Of Participants Experiencing Treatment-emergent Adverse Events Adverse Event Leading to Withdrawal from Treatment	6 participants	1 participants	0 participants	2 participants	0 participants	1 participants	4 participants	0 participants
Number Of Participants Experiencing Treatment-emergent Adverse Events All-Cause Mortality	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number Of Participants Experiencing Treatment-emergent Adverse Events Serious Adverse Events	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number Of Participants Experiencing Treatment-emergent Adverse Events Participants With Any Adverse Event	8 participants	8 participants	6 participants	8 participants	4 participants	8 participants	9 participants	12 participants
Number Of Participants Experiencing Treatment-emergent Adverse Events Participants With Any Adverse Events During Single Dose	8 participants	6 participants	2 participants	3 participants	3 participants	4 participants	8 participants	5 participants
Number Of Participants Experiencing Treatment-emergent Adverse Events Participants With Any Adverse Event During Multiple Doses	7 participants	8 participants	6 participants	7 participants	3 participants	8 participants	8 participants	12 participants

SECONDARY outcome

Timeframe: Day 1 (Measurements taken at 1 [end of infusion], 2, 4, 8, 12, 18, 24, 36, 48, and 72 hours after the start of dosing)

Population: Cohort 3 PK samples were not analyzed due to early termination of the cohort. The number of participants analyzed reflects the actual number of participants with PK measurements taken at Day 1.

Assessment of AUC0-t by cohort after a single intravenous dose of Minocin (minocycline) for Injection on Day 1 is reported as mg times hour/liter (mg\*h/L).

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=9 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=8 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment of Area Under The Concentration-time Curve From Zero Hours To The Last Measured Concentration (AUC0-t) After A Single Dose Of Minocin On Day 1	51.49 mg*h/L Standard Deviation 20.0	78.98 mg*h/L Standard Deviation 28.2	8.66 mg*h/L Standard Deviation 1.6	24.0 mg*h/L Standard Deviation 6.5	37.35 mg*h/L Standard Deviation 13.9	59.79 mg*h/L Standard Deviation 16.0	—	—

SECONDARY outcome

Timeframe: Day 4 (Measurements taken at 1 [end of infusion], 2, 4, 8, and 12 hours after the start of dosing)

Assessment of AUC0-t by cohort after a single dose of Minocin (minocycline) for Injection using plasma from serial blood samples on Day 4 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=8 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=7 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=7 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4	27.86 mg*h/L Standard Deviation 10.0	42.83 mg*h/L Standard Deviation 19.3	5.12 mg*h/L Standard Deviation 0.9	11.69 mg*h/L Standard Deviation 2.6	20.04 mg*h/L Standard Deviation 7.8	28.54 mg*h/L Standard Deviation 7.8	—	—

SECONDARY outcome

Timeframe: Day 11 (Measurements taken at 1 [end of infusion], 2, 4, 8, 12, 18, 24, 36, 48, and 72 hours after the start of dosing)

Population: Cohort 3 and Cohort 4 PK samples were not taken at Day 11 due to early termination of the cohorts. The number of participants analyzed reflects the actual number of participants with PK measurements taken at Day 11.

Assessment of AUC0-t by cohort after 7 days of multiple doses of Minocin (minocycline) for Injection using plasma from serial blood samples on Day 11 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=4 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=6 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=6 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=7 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=7 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On Day 11	119.0 mg*h/L Standard Deviation 56.3	—	27.5 mg*h/L Standard Deviation 5.5	80.7 mg*h/L Standard Deviation 19.9	173.7 mg*h/L Standard Deviation 100.9	124.1 mg*h/L Standard Deviation 50.2	—	—

SECONDARY outcome

Timeframe: Day 1 (Measurements taken at 1 [end of infusion], 2, 4, 8, 12, 18, 24, 36, 48, and 72 hours after the start of dosing)

Population: Cohort 3 PK samples were not analyzed due to early termination of cohort. The number of participants analyzed reflects the number of participants who had plasma PK samples taken at Day 1.

Assessment of Cmax by cohort for a single intravenous dose of Minocin (minocycline) for Injection using serial blood samples on Day 1 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=8 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=8 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On Day 1	4.36 mg/L Standard Deviation 0.9	7.03 mg/L Standard Deviation 2.4	0.99 mg/L Standard Deviation 0.2	1.89 mg/L Standard Deviation 0.4	3.35 mg/L Standard Deviation 1.2	4.93 mg/L Standard Deviation 1.9	—	—

SECONDARY outcome

Timeframe: Day 4 (Measurements taken at 1 [end of infusion], 2, 4, 8, and 12 hours after the start of dosing)

Assessment of Cmax by cohort for a single intravenous dose of Minocin (minocycline) for Injection using serial blood samples on Day 4 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=8 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=7 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=7 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4	5.14 mg/L Standard Deviation 1.3	6.51 mg/L Standard Deviation 2.5	0.96 mg/L Standard Deviation 0.23	2.05 mg/L Standard Deviation 0.5	3.52 mg/L Standard Deviation 1.6	4.49 mg/L Standard Deviation 0.8	—	—

SECONDARY outcome

Timeframe: Day 11 (Measurements taken at 1 [end of infusion], 2, 4, 8, 12, 18, 24, 36, 48, and 72 hours after the start of dosing)

Assessment of Cmax by cohort after 7 days of twice daily dosing of Minocin (minocycline) for Injection using serial blood samples on Day 11 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=4 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=6 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=6 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=7 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=7 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11	6.17 mg/L Standard Deviation 1.7	—	1.71 mg/L Standard Deviation 0.2	4.59 mg/L Standard Deviation 1.1	8.91 mg/L Standard Deviation 4.5	7.58 mg/L Standard Deviation 2.4	—	—

SECONDARY outcome

Timeframe: Day 1 (Measurements taken at 1 [end of infusion], 2, 4, 8, 12, 18, 24, 36, 48, and 72 hours after the start of dosing)

Assessment of T1/2, defined by T1/2 = natural log of 2 divided by elimination constant (Kel) (T1/2), by cohort after a single intravenous dose of Minocin (minocycline) for Injection on Day 1 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=9 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=8 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of Apparent Terminal Elimination Half-life (T1/2) By Cohort For A Single Dose Of Minocin Using Plasma From Serial Blood Samples On Day 1	14.44 h Standard Deviation 2.7	17.27 h Standard Deviation 3.6	11.05 h Standard Deviation 2.1	13.70 h Standard Deviation 2.3	16.62 h Standard Deviation 3.9	17.55 h Standard Deviation 2.1	—	—

SECONDARY outcome

Timeframe: Day 11 (Measurements taken at 1 [end of infusion], 2, 4, 8, 12, 18, 24, 36, 48, and 72 hours after the start of dosing)

Assessment of T1/2, defined by T1/2 = natural log of 2 divided by Kel (T1/2), by cohort after 7 days of twice daily dosing of intravenous doses of Minocin (minocycline) for Injection on Day 11 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=4 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=6 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=6 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=7 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=7 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of T1/2 By Cohort After Multiple Doses Of Minocin Using Plasma From Serial Blood Samples On Day 11	20.19 h Standard Deviation 4.2	—	15.89 h Standard Deviation 2.8	18.22 h Standard Deviation 2.4	19.78 h Standard Deviation 3.4	18.15 h Standard Deviation 1.4	—	—

SECONDARY outcome

Timeframe: Day 1 (Measurements collected from 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72 hours after the start of dosing

Assessment of amount of drug excreted in urine after a single intravenous dose of Minocin (minocycline) for Injection using serial urine samples on Day 1 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=9 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=8 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1	0.40 L/h Standard Deviation 0.09	0.37 L/h Standard Deviation 0.13	0.37 L/h Standard Deviation 0.17	0.37 L/h Standard Deviation 0.04	0.38 L/h Standard Deviation 0.13	0.34 L/h Standard Deviation 0.10	—	—

SECONDARY outcome

Timeframe: Day 11 (Measurements collected from 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72 hours after the start of dosing

Population: Cohort 3 and Cohort 4 PK samples were not taken at Day 11 at Day 11 due to early termination of the cohorts. The number of participants analyzed reflects the actual number of participants with urine samples taken at Day 11.

Assessment of amount of drug excreted in urine after 7 days of twice daily intravenous doses of Minocin (minocycline) for Injection using serial urine samples on Day 11 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=4 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=6 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=6 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=7 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=7 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of Amount Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11	0.43 L/hr Standard Deviation 0.22	—	0.47 L/hr Standard Deviation 0.10	0.35 L/hr Standard Deviation 0.10	0.28 L/hr Standard Deviation 0.09	0.35 L/hr Standard Deviation 0.10	—	—

SECONDARY outcome

Timeframe: Day 1 (Measurements collected from 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72 hours after the start of dosing)

Assessment of percent of dose excreted in urine after a single intravenous dose of Minocin (minocycline) for Injection using serial urine samples on Day 1 is reported.

Outcome measures

Outcome measures
Measure	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 6 n=9 Participants 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Cohort 1 n=8 Participants 100 mg of Minocin (minocycline) for Injection on Day 1 then 100 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 2 n=8 Participants 200 mg of Minocin (minocycline) for Injection on Day 1 then 200 mg every 12 hours on Days 4 to 10 and a single dose on Day 11	Cohort 3b n=8 Participants 300 mg of Minocin (minocycline) for Injection on Day 1 then 300 mg every 12 hours on Days 4 to 10 and a single dose on Day 11 Replacement of Cohort 3	Cohort 5 n=8 Participants 500 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 500 mg loading dose as the first dose on Day 4, 300 mg every 12 hours on Days 4 to 10 and as a single dose Day 11	Cohort 6 600 mg of Minocin (minocycline) for Injection as a single dose on Day 1, 600 mg loading dose as the first dose on Day 4, 300 mg every 12 hours Days 4 to 10 and as a single dose on Day 11	Placebo Placebo was in the form of the same 100-mL bags of normal saline (0.9% Sodium Chloride Injection USP). Dosing was to the same schedule as participants randomized to Minocin (minocycline) for Injection.
Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1	4.05 percentage of dose Standard Deviation 0.50	4.67 percentage of dose Standard Deviation 1.12	3.56 percentage of dose Standard Deviation 1.54	4.73 percentage of dose Standard Deviation 1.13	4.58 percentage of dose Standard Deviation 0.82	4.98 percentage of dose Standard Deviation 0.62	—	—

SECONDARY outcome

Timeframe: Day 11 (Measurements collected from 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72 hours after the start of dosing

Assessment of percentage of drug excreted in urine after 7 days of twice daily intravenous doses of Minocin (minocycline) for Injection using serial urine samples on Day 11 is reported.