Normal Healthy Volunteers
Conditions
Keywords
Bacterial infections
Brief summary
This was a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study of the safety, tolerability, and pharmacokinetics of Minocin (minocycline) for injection in healthy adult participants.
Detailed description
The purpose of this study was to collect safety, tolerability, and pharmacokinetic (PK) data on ascending dose regimens of Minocin (minocycline) for Injection. The safety, tolerability, and PK data was to support the compound as a potential clinical candidate in Europe and allow recommendations of dose levels to be used in future Phase 2/3 studies.
Interventions
Intravenous formulation of minocycline, a derivative of tetracycline
OTHERPlacebo
Placebo - Normal Saline
Sponsors
Universitätsklinikum Köln
Innovative Medicines Initiative
Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Model Description: Cohorts 1 and 2 were run concurrently as they were using the approved doses of intravenous minocycline in the United States. Cohorts 3, 4, 5 and 6 were run sequentially and only after review of data from the preceding cohorts by the data monitoring committee.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. A signed informed consent form, the ability to understand the study conduct and tasks that were required for study participation, and a willingness to cooperate with all tasks, tests, and examinations as required by the protocol, whether in the research unit or after discharge, for the duration of the study 2. Male or female between 18 and 50 years of age inclusive 3. Participant had a body mass index ≥18 kilograms/square meter (kg/m\^2) and ≤30 kg/m\^2. 4. Participant was non-smoker or smokes up to 5 cigarettes per day (or equivalent). 5. Participant was in good health based on medical history and physical examination findings and had no clinically meaningful safety laboratory abnormalities (hematology, blood chemistry, and urinalysis) or 12-lead electrocardiogram results, as assessed by the Principal Investigator. 6. Vital signs (blood pressure, pulse, respiratory rate and temperature) measured at screening/baseline must have been within the following ranges: systolic blood pressure ≥90 to ≤150 millimeters of mercury (mm Hg), diastolic blood pressure ≥45 to ≤90 mm Hg; heart rate ≥45 to ≤90 beats per minute (taken after resting in a supine position for at least 5 minutes). 7. Expectation that intravenous access would be sufficient to allow for ease of study drug infusion, and for all protocol-required blood sampling to take place 8. Participant committed to remaining admitted in the research unit for the course of the study. 9. Female participant was surgically sterile, postmenopausal: period of amenorrhea for at least 2 years, or if of childbearing potential, agreed to abstinence or to use at least 2 acceptable methods of birth control (for example prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, barrier methods) or male partner sterilization alone, between the first dose (Day 1) and for 90 days after the completion of the study.
Exclusion criteria
1. Had any condition, including findings in the medical history or in pre-study assessments that constituted a risk or a contraindication for the participation in the study or completing the study 2. Positive breath test for alcohol and/or positive urine test for drugs of abuse at Screening and Day -1 Visits 3. Had a history or presence of alcohol/drug abuse within 2 years. Alcohol abuse was defined as regularly consuming \>3 units/day (21 units per week for men), \>2 units/day (14 units/week) for women. A unit was defined as a can of 4% beer (330 mL), approximately 190 mL of 6-7% beer (malt liquor), a glass of 40% spirits (30 mL), a glass of wine (100 mL). 4. Participant showed positive hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus I/II antibodies and antigen tests. 5. Participant had active or ongoing candida infection. 6. Blood or plasma donation within past 2 months 7. Females who were pregnant or nursing or who had a positive pregnancy test result at the Screening Visit or Day -1 prior to dosing 8. Males who were unwilling to practice abstinence or use an acceptable method of birth control during the entire study period and for 90 days after the completion of the study (that is condom with spermicide, where locally available) 9. Presence of known raised intracranial pressure 10. Use of retinoids (for example, isotretinoin) 11. History of significant hypersensitivity or allergic reaction to any of the tetracycline class of antibiotics or the components of those antibiotics 12. Receipt of any investigational medication or investigational device during the last 30 days prior to randomization 13. Treatment with any prescription, vitamins or over-the-counter drugs, within 2 weeks or five half-lives, whichever was longer, or herbal nutritional supplements within 2 weeks of screening, with the exception of acetaminophen/paracetamol for minor headache. Participants were not allowed to receive medications for the duration of the study (except the abovementioned acetaminophen/paracetamol). Birth control or other hormone replacement were also permitted as long as it had been taken at a stable dose for at least 3 months before the Screening Visit and remained stable for the duration of the study. 14. A corrected QT interval by Fridericia \>480 milliseconds 15. Calculated creatinine clearance less than 50 mL/minute (Cockcroft-Gault method) at screening or check-in (Day -1) 16. Unable or unwilling, in the judgment of the Investigator, to comply with the protocol 17. An employee of the Investigator, the study center, the sponsor or The Medicines Company with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, or a family member of the employee or the Investigator 18. Prior enrollment in any minocycline study including prior cohorts in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants Experiencing Treatment-emergent Adverse Events | Day 1 through Day 17 | Safety and tolerability of single and multiple intravenous doses of Minocin (minocycline) for Injection assessed by number of participants with adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4 | 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. |
| Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On Day 11 | 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 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. |
| Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On Day 1 | 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 Cmax by cohort for a single intravenous dose of Minocin (minocycline) for Injection using serial blood samples on Day 1 is reported. |
| Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4 | 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. |
| Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11 | 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. |
| 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 | 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 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). |
| Assessment Of T1/2 By Cohort After Multiple Doses Of Minocin Using Plasma From Serial Blood Samples On Day 11 | 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. |
| Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 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. |
| Assessment Of Amount Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 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 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. |
| Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 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. |
| Assessment Of Percentage Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 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. |
| 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 | 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. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 100 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 | 8 |
| 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 | 8 |
| 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. | 6 |
| 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 | 8 |
| 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 | 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 | 8 |
| 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 | 9 |
| 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. | 14 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 1 | 6 | 1 | 4 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 6 | 0 | 2 | 0 | 0 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 2 | Total | Placebo | Cohort 6 | Cohort 5 | Cohort 4 | Cohort 1 | Cohort 3b | Cohort 3 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.00 years STANDARD_DEVIATION 7.45 | 28.06 years STANDARD_DEVIATION 8.65 | 27.43 years STANDARD_DEVIATION 8.23 | 30.56 years STANDARD_DEVIATION 12.12 | 25.75 years STANDARD_DEVIATION 8.76 | 29.63 years STANDARD_DEVIATION 8.72 | 26.63 years STANDARD_DEVIATION 7.76 | 25.00 years STANDARD_DEVIATION 7.45 | 28.83 years STANDARD_DEVIATION 9.75 |
| Body Mass Index | 23.2 kilogram/square meter STANDARD_DEVIATION 2.7 | 22.8 kilogram/square meter STANDARD_DEVIATION 2.7 | 22.1 kilogram/square meter STANDARD_DEVIATION 2.8 | 23.4 kilogram/square meter STANDARD_DEVIATION 3 | 22.9 kilogram/square meter STANDARD_DEVIATION 2.5 | 22.7 kilogram/square meter STANDARD_DEVIATION 2.9 | 23.3 kilogram/square meter STANDARD_DEVIATION 2.6 | 22.5 kilogram/square meter STANDARD_DEVIATION 2.4 | 22.5 kilogram/square meter STANDARD_DEVIATION 3.4 |
| Height | 175.8 centimeter STANDARD_DEVIATION 7.6 | 177.7 centimeter STANDARD_DEVIATION 8.9 | 178.1 centimeter STANDARD_DEVIATION 10.1 | 176.4 centimeter STANDARD_DEVIATION 11 | 178.0 centimeter STANDARD_DEVIATION 6 | 175.4 centimeter STANDARD_DEVIATION 9.2 | 179.3 centimeter STANDARD_DEVIATION 9.8 | 178.1 centimeter STANDARD_DEVIATION 7.1 | 181.36 centimeter STANDARD_DEVIATION 11.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 63 Participants | 14 Participants | 7 Participants | 6 Participants | 7 Participants | 8 Participants | 8 Participants | 6 Participants |
| Region of Enrollment Netherlands | 8 participants | 69 participants | 14 participants | 9 participants | 8 participants | 8 participants | 8 participants | 8 participants | 6 participants |
| Sex: Female, Male Female | 3 Participants | 25 Participants | 7 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 44 Participants | 7 Participants | 5 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants |
| Weight | 71.7 kilogram STANDARD_DEVIATION 9 | 72.1 kilogram STANDARD_DEVIATION 11 | 70.9 kilogram STANDARD_DEVIATION 14.6 | 73.0 kilogram STANDARD_DEVIATION 12.7 | 72.6 kilogram STANDARD_DEVIATION 8 | 69.9 kilogram STANDARD_DEVIATION 11.6 | 75.1 kilogram STANDARD_DEVIATION 10.6 | 71.6 kilogram STANDARD_DEVIATION 10.1 | 73.4 kilogram STANDARD_DEVIATION 10.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 14 |
| other Total, other adverse events | 6 / 8 | 8 / 8 | 4 / 6 | 8 / 8 | 8 / 8 | 8 / 8 | 9 / 9 | 12 / 14 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 14 |
Outcome results
Primary
Number Of Participants Experiencing Treatment-emergent Adverse Events
Safety and tolerability of single and multiple intravenous doses of Minocin (minocycline) for Injection assessed by number of participants with adverse events.
Time frame: Day 1 through Day 17
Population: Safety Population: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 6 participants |
| Cohort 1 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 6 participants |
| Cohort 1 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Cohort 1 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 0 participants |
| Cohort 1 | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
| Cohort 1 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 2 participants |
| Cohort 2 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 2 participants |
| Cohort 2 | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
| Cohort 2 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 7 participants |
| Cohort 2 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Cohort 2 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 3 participants |
| Cohort 2 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 8 participants |
| Cohort 3 | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
| Cohort 3 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 3 participants |
| Cohort 3 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 4 participants |
| Cohort 3 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 3 participants |
| Cohort 3 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 0 participants |
| Cohort 3 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Cohort 3b | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 4 participants |
| Cohort 3b | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
| Cohort 3b | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 1 participants |
| Cohort 3b | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 8 participants |
| Cohort 3b | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Cohort 3b | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 8 participants |
| Cohort 4 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 6 participants |
| Cohort 4 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 8 participants |
| Cohort 4 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Cohort 4 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 8 participants |
| Cohort 4 | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
| Cohort 4 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 7 participants |
| Cohort 5 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 1 participants |
| Cohort 5 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 6 participants |
| Cohort 5 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Cohort 5 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 8 participants |
| Cohort 5 | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
| Cohort 5 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 8 participants |
| Cohort 6 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 9 participants |
| Cohort 6 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 8 participants |
| Cohort 6 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 8 participants |
| Cohort 6 | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
| Cohort 6 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 4 participants |
| Cohort 6 | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Placebo | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event During Multiple Doses | 12 participants |
| Placebo | Number Of Participants Experiencing Treatment-emergent Adverse Events | Serious Adverse Events | 0 participants |
| Placebo | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Event | 12 participants |
| Placebo | Number Of Participants Experiencing Treatment-emergent Adverse Events | Participants With Any Adverse Events During Single Dose | 5 participants |
| Placebo | Number Of Participants Experiencing Treatment-emergent Adverse Events | Adverse Event Leading to Withdrawal from Treatment | 0 participants |
| Placebo | Number Of Participants Experiencing Treatment-emergent Adverse Events | All-Cause Mortality | 0 participants |
Secondary
Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1
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.
Time frame: Day 1 (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 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 0.37 L/h | Standard Deviation 0.17 |
| Cohort 2 | Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 0.37 L/h | Standard Deviation 0.04 |
| Cohort 3 | Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 0.38 L/h | Standard Deviation 0.13 |
| Cohort 3b | Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 0.34 L/h | Standard Deviation 0.1 |
| Cohort 4 | 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 |
| Cohort 5 | Assessment Of Amount Of Drug Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 0.37 L/h | Standard Deviation 0.13 |
Secondary
Assessment Of Amount Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of Amount Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 0.47 L/hr | Standard Deviation 0.1 |
| Cohort 2 | Assessment Of Amount Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 0.35 L/hr | Standard Deviation 0.1 |
| Cohort 3 | Assessment Of Amount Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 0.28 L/hr | Standard Deviation 0.09 |
| Cohort 3b | Assessment Of Amount Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 0.35 L/hr | Standard Deviation 0.1 |
| Cohort 4 | 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 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 | 11.05 h | Standard Deviation 2.1 |
| Cohort 2 | 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 | 13.70 h | Standard Deviation 2.3 |
| Cohort 3 | 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 | 16.62 h | Standard Deviation 3.9 |
| Cohort 3b | 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 | 17.55 h | Standard Deviation 2.1 |
| Cohort 4 | 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 |
| Cohort 5 | 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 | 17.27 h | Standard Deviation 3.6 |
Secondary
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
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 | 8.66 mg*h/L | Standard Deviation 1.6 |
| Cohort 2 | 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 | 24.0 mg*h/L | Standard Deviation 6.5 |
| Cohort 3 | 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 | 37.35 mg*h/L | Standard Deviation 13.9 |
| Cohort 3b | 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 | 59.79 mg*h/L | Standard Deviation 16 |
| Cohort 4 | 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 |
| Cohort 5 | 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 | 78.98 mg*h/L | Standard Deviation 28.2 |
Secondary
Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4
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.
Time frame: Day 4 (Measurements taken at 1 [end of infusion], 2, 4, 8, and 12 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 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4 | 5.12 mg*h/L | Standard Deviation 0.9 |
| Cohort 2 | Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4 | 11.69 mg*h/L | Standard Deviation 2.6 |
| Cohort 3 | Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4 | 20.04 mg*h/L | Standard Deviation 7.8 |
| Cohort 3b | Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4 | 28.54 mg*h/L | Standard Deviation 7.8 |
| Cohort 4 | Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4 | 27.86 mg*h/L | Standard Deviation 10 |
| Cohort 5 | Assessment Of AUC0-t By Cohort After A Single Dose Of Minocin On Day 4 | 42.83 mg*h/L | Standard Deviation 19.3 |
Secondary
Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On Day 11 | 27.5 mg*h/L | Standard Deviation 5.5 |
| Cohort 2 | Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On Day 11 | 80.7 mg*h/L | Standard Deviation 19.9 |
| Cohort 3 | Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On Day 11 | 173.7 mg*h/L | Standard Deviation 100.9 |
| Cohort 3b | Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On Day 11 | 124.1 mg*h/L | Standard Deviation 50.2 |
| Cohort 4 | Assessment Of AUC0-t By Cohort After Multiple Doses Of Minocin On Day 11 | 119.0 mg*h/L | Standard Deviation 56.3 |
Secondary
Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4
Assessment of Cmax by cohort for a single intravenous dose of Minocin (minocycline) for Injection using serial blood samples on Day 4 is reported.
Time frame: Day 4 (Measurements taken at 1 [end of infusion], 2, 4, 8, and 12 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 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4 | 0.96 mg/L | Standard Deviation 0.23 |
| Cohort 2 | Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4 | 2.05 mg/L | Standard Deviation 0.5 |
| Cohort 3 | Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4 | 3.52 mg/L | Standard Deviation 1.6 |
| Cohort 3b | Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4 | 4.49 mg/L | Standard Deviation 0.8 |
| Cohort 4 | Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4 | 5.14 mg/L | Standard Deviation 1.3 |
| Cohort 5 | Assessment of Cmax by Cohort for a Single Dose of Minocin on Day 4 | 6.51 mg/L | Standard Deviation 2.5 |
Secondary
Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11 | 1.71 mg/L | Standard Deviation 0.2 |
| Cohort 2 | Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11 | 4.59 mg/L | Standard Deviation 1.1 |
| Cohort 3 | Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11 | 8.91 mg/L | Standard Deviation 4.5 |
| Cohort 3b | Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11 | 7.58 mg/L | Standard Deviation 2.4 |
| Cohort 4 | Assessment Of Cmax By Cohort For Multiple Doses Of Minocin On Day 11 | 6.17 mg/L | Standard Deviation 1.7 |
Secondary
Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On Day 1 | 0.99 mg/L | Standard Deviation 0.2 |
| Cohort 2 | Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On Day 1 | 1.89 mg/L | Standard Deviation 0.4 |
| Cohort 3 | Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On Day 1 | 3.35 mg/L | Standard Deviation 1.2 |
| Cohort 3b | Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On Day 1 | 4.93 mg/L | Standard Deviation 1.9 |
| Cohort 4 | 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 |
| Cohort 5 | Assessment Of Maximum Plasma Concentration (Cmax) By Cohort For A Single Dose Of Minocin On Day 1 | 7.03 mg/L | Standard Deviation 2.4 |
Secondary
Assessment Of Percentage Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11
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.
Time frame: 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 due to early termination of the cohorts. The number of participants analyzed reflects the actual number of participants with urine PK samples taken at Day 11.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of Percentage Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 5.86 Percentage of dose | Standard Deviation 0.63 |
| Cohort 2 | Assessment Of Percentage Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 5.80 Percentage of dose | Standard Deviation 1.27 |
| Cohort 3 | Assessment Of Percentage Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 5.92 Percentage of dose | Standard Deviation 0.72 |
| Cohort 3b | Assessment Of Percentage Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 6.13 Percentage of dose | Standard Deviation 1.53 |
| Cohort 4 | Assessment Of Percentage Of Drug Excreted In Urine After Multiple Intravenous Doses Of Minocin Using Serial Urine Samples On Day 11 | 6.09 Percentage of dose | Standard Deviation 1.23 |
Secondary
Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1
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.
Time frame: Day 1 (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 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 3.56 percentage of dose | Standard Deviation 1.54 |
| Cohort 2 | Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 4.73 percentage of dose | Standard Deviation 1.13 |
| Cohort 3 | Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 4.58 percentage of dose | Standard Deviation 0.82 |
| Cohort 3b | Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 4.98 percentage of dose | Standard Deviation 0.62 |
| Cohort 4 | 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 0.5 |
| Cohort 5 | Assessment Of Percent of Dose Excreted In Urine After A Single Dose Of Minocin Using Serial Urine Samples On Day 1 | 4.67 percentage of dose | Standard Deviation 1.12 |
Secondary
Assessment Of T1/2 By Cohort After Multiple Doses Of Minocin Using Plasma From Serial Blood Samples On Day 11
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Assessment Of T1/2 By Cohort After Multiple Doses Of Minocin Using Plasma From Serial Blood Samples On Day 11 | 15.89 h | Standard Deviation 2.8 |
| Cohort 2 | Assessment Of T1/2 By Cohort After Multiple Doses Of Minocin Using Plasma From Serial Blood Samples On Day 11 | 18.22 h | Standard Deviation 2.4 |
| Cohort 3 | Assessment Of T1/2 By Cohort After Multiple Doses Of Minocin Using Plasma From Serial Blood Samples On Day 11 | 19.78 h | Standard Deviation 3.4 |
| Cohort 3b | Assessment Of T1/2 By Cohort After Multiple Doses Of Minocin Using Plasma From Serial Blood Samples On Day 11 | 18.15 h | Standard Deviation 1.4 |
| Cohort 4 | 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 |