Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Minocin (Minocycline) for Injection in Healthy Adults
Condition: Normal Healthy Volunteers
Intervention: Minocin (minocycline) for Injection; Placebo
Intervention description: Intravenous formulation of minocycline, a derivative of tetracycline; Placebo - Normal Saline
Intervention MeSH terms: Minocycline
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bacterial infections

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.
    

Eligibility criteria:

        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