Evaluate Safety and Pharmacokinetics of Minocin (Minocycline) for Injection in Subjects With Renal Insufficiency
Condition: Renal Insufficiency, Acute; Renal Insufficiency, Chronic; Healthy Subjects
MeSH terms: Renal Insufficiency; Renal Insufficiency, Chronic; Acute Kidney Injury
Intervention: Minocin (minocycline) for Injection
Intervention description: 200mg IV Minocin given over 1 hour
Intervention MeSH terms: Minocycline
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bacterial infections

Summary:

      This is a Phase 1, open-label, single-dose study of the safety, tolerability, and
      pharmacokinetics of Minocin® (minocycline) for injection in subjects with renal
      insufficiency.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A signed informed consent form, the ability to understand the study conduct and tasks
             that are required for study participation, and a willingness to cooperate with all
             tasks, tests, and examinations as required by the protocol, whether in the hospital or
             after discharge, for the duration of the study;

          2. Healthy adult male or female between 18 and 85 years of age (inclusive) at the time of
             screening;

          3. Subject has a body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 45 kg/m2;

          4. Pulse measured at screening/baseline must be within the ranges ≥ 45 to ≤ 115 beats per
             minute (bpm, taken after resting in a semi-recumbent position for at least 5 minutes);

          5. Have sufficient peripheral vascular access, based on the Investigator's assessment,
             for all blood sample collections to take place;

          6. Female subject is surgically sterile, postmenopausal, or if of childbearing potential,
             agrees to abstinence or to use at least 2 acceptable methods of birth control (e.g.,
             prescription oral contraceptives, contraceptive injections, contraceptive patch,
             intrauterine device, barrier methods, etc.) or male partner sterilization alone,
             between randomization and for 7 days after the completion of the study;

             Subjects with Renal Insufficiency:

          7. Assessment of renal insufficiency for assignment to study groups will be based on
             measurements of estimated glomerular filtration rate calculated by the Modification of
             Diet in Renal Disease equation at the screening visit to determine eligibility;

             Subjects with Normal Renal Function:

          8. Normal volunteers first matched by age (± 10 years), BMI (± 20%), and gender to the
             mean values of the moderate renal insufficiency group. Once the mild, moderate, and
             severe renal insufficiency groups are fully enrolled, the mean values of age, BMI, and
             gender will be calculated for the pooled renal insufficiency groups, and additional
             healthy subjects may be enrolled to match the pooled means;

          9. Have a creatinine clearance (CrCl) ≥ 90 mL/min calculated using the Cockcroft Gault
             equation;

             Hemodialysis Subjects:

         10. Receiving stable hemodialysis (Kt/V > 1.2) at least 3 times a week for at least 3
             months, using an arteriovenous fistula or graft;

         11. Otherwise considered to be clinically stable with respect to underlying renal
             impairment, as determined by the Investigator, and based upon a medical evaluation
             that includes a medical history, physical examination, laboratory tests, and
             electrocardiogram (ECG);

         12. Have clinical laboratory test results that are considered clinically stable in the
             opinion of the Investigator, especially if the clinical abnormality or laboratory
             parameter is deemed associated with the subject's underlying renal impairment;

         13. A stable medication regimen is required, defined as not starting new drug(s) or
             significant changes in dosage(s) within 14 days prior to administration of study drug,
             or during the conduct of the study. Changes of medications in hemodialysis subjects
             are subject to dialysis site protocols such that erythropoiesis-stimulating agents,
             iron, and vitamin D can be changed based on the then current subject status and
             dialysis unit standard practice and subject safety prior to screening.

        Exclusion Criteria:

          1. Has any condition, including findings in the medical history or in pre-study
             assessments, that are capable of altering the distribution, metabolism, or elimination
             of drugs or that constitute a risk or a contraindication for the participation in the
             study or completing the study; Subjects in the renal insufficiency groups will have
             consideration for the degree of renal insufficiency and presence of comorbidities;

          2. Current evidence or history of malignancy, excluding basal cell carcinoma, in the 2
             years prior to Day -1 (day before dosing) with no evidence of recurrence;

          3. Blood or plasma donation within past 2 months;

          4. Vigorous exercise from 48 hours prior to Day -1 until the day of discharge from the
             study;

          5. Surgery within 48 hours prior to randomization or surgery planned during the study
             period;

          6. Liver function abnormalities at screening (or Day -1) (defined by an elevation in
             bilirubin, aspartate aminotransferase, or alanine aminotransferase that is 1.5 x upper
             limit of normal of the normal range for subjects based on age and sex);

          7. Females who are pregnant or nursing or who have a positive pregnancy test result;

          8. Males who are unwilling to practice abstinence or use an acceptable method of birth
             control during the entire study period (i.e., condom with spermicide, where locally
             available);

          9. Presence of known raised intracranial pressure;

         10. Use of isotretinoin;

         11. History of significant hypersensitivity or allergic reaction to tetracycline
             antibiotics;

         12. History of seizures (e.g., epilepsy), head injury, or meningitis requiring ongoing
             anti-seizure medications;

         13. Receipt of any investigational medication or investigational device during the last 30
             days prior to randomization;

         14. A corrected QT (Fridericia) > 500 msec or history of prolonged QT syndrome;

         15. Use of products containing alcohol, caffeine, xanthine, or ephedrine within 48 hours
             before dosing;

         16. Unable or unwilling, in the judgment of the Investigator, to comply with the protocol;

         17. Subjects that have known active hepatitis B or C, or human immunodeficiency virus
             (HIV) infection or have known immune deficiency disease at screening;

         18. Concurrent use of medications known to affect the elimination of serum creatinine
             (e.g., trimethoprim/sulfamethoxazole [Bactrim®] or cimetidine [Tagamet®]) and
             competitors of renal tubular secretion (e.g., probenecid) within 30 days prior to the
             first dose of study drug or anticipated need for these therapies through the last PK
             sample;

         19. An employee of the Investigator or study center or sponsor, with direct involvement in
             the proposed study or other studies under the direction of that Investigator or study
             center or the Sponsor, or a family member of the employee or the Investigator.

             Subjects with Renal Insufficiency:

         20. Have a sitting systolic blood pressure (BP) > 180 mm Hg or < 90 mm Hg or have a
             sitting diastolic BP > 110 mm Hg or < 50 mm Hg at the screening visit;

         21. Use of any other prescription or nonprescription drugs, vitamins,
             grapefruit/grapefruit juice, or dietary or herbal supplements within 14 days prior to
             Day -1 other than those listed below:

               1. Medications required to treat underlying renal disease or medical conditions
                  related to renal disease are permitted;

               2. Oral contraceptives are permitted for birth control;

               3. Doses of concomitant medications (except hormonal contraceptives, hormone
                  replacement therapy for females, and insulin) must be stable for 3 weeks prior to
                  dosing on Day 1. Minor dose changes consistent with treatment practices may be
                  permitted at the discretion of the Sponsor's Medical Monitor;

               4. Acetaminophen (≤ 1 g/day) and low dose acetylsalicylic acid (ASA, e.g., ≤ 325 mg
                  per day) are permitted.

             Subjects with Normal Renal Function:

         22. Abnormal and clinically significant findings on physical examination, medical history,
             serum chemistry, hematology, or urinalysis per Investigator discretion;

         23. Have a sitting systolic BP > 150 mm Hg or < 90 mm Hg or have a sitting diastolic BP >
             90 mm Hg or < 50 mm Hg at the screening visit;

         24. CrCl < 90 mL/min calculated using the Cockcroft Gault equation;

         25. Use of any prescription or nonprescription drugs, vitamins, grapefruit/grapefruit
             juice, or dietary or herbal supplements within 14 days prior to Day -1 other than
             those listed below:

               1. Oral contraceptives are permitted for birth control;

               2. Acetaminophen (≤ 1 g/day) and low dose ASA (i.e., ≤ 325 mg per day) are
                  permitted.