Evaluate Safety and Pharmacokinetics of Minocin (Minocycline) for Injection in Subjects With Renal Insufficiency

NCT02808052 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: MDCO-MIN-16-03702
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Insufficiency, Acute; Renal Insufficiency, Chronic; Healthy Subjects

Keywords

Bacterial infections

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of Intravenous Dose(s) of Minocin (Minocycline) for Injection Assessed by Number of Subjects With Adverse Events

  Safety and Tolerability: Subjects with mild, moderate, or severe renal insufficiency with any adverse events, any serious adverse events, any study related adverse events, and any adverse events with a fatal outcome.

  Approximately 24 weeks

Study Arms (1)

Minocin (minocycline) for Injection

EXPERIMENTAL

Minocin (minocycline) for Injection will be supplied as a sterile lyophilized powder in single-use 10-mL glass vials. Each vial contains 108 mg of minocycline hydrochloride equivalent to 100 mg of minocycline. Each cohort receives a single 200-mg dose of Minocin (minocycline) for Injection except for the hemodialysis therapy/end stage renal disease cohort, which receives two 200-mg doses.

Drug: Minocin (minocycline) for Injection

Interventions

Minocin (minocycline) for Injection DRUG

200mg IV Minocin given over 1 hour

Also known as: Minocin, minocycline

Minocin (minocycline) for Injection

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Healthy adult male or female between 18 and 85 years of age (inclusive) at the time of screening;
• Subject has a body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 45 kg/m2;
• 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);
• Have sufficient peripheral vascular access, based on the Investigator's assessment, for all blood sample collections to take place;
• 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:
• 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:
• 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;
• Have a creatinine clearance (CrCl) ≥ 90 mL/min calculated using the Cockcroft Gault equation;
• Hemodialysis Subjects:
• Receiving stable hemodialysis (Kt/V \> 1.2) at least 3 times a week for at least 3 months, using an arteriovenous fistula or graft;
• 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);
• 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;

You may not qualify if:

• 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;
• 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;
• Blood or plasma donation within past 2 months;
• Vigorous exercise from 48 hours prior to Day -1 until the day of discharge from the study;
• Surgery within 48 hours prior to randomization or surgery planned during the study period;
• 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);
• Females who are pregnant or nursing or who have a positive pregnancy test result;
• 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);
• Presence of known raised intracranial pressure;
• Use of isotretinoin;
• History of significant hypersensitivity or allergic reaction to tetracycline antibiotics;
• History of seizures (e.g., epilepsy), head injury, or meningitis requiring ongoing anti-seizure medications;
• Receipt of any investigational medication or investigational device during the last 30 days prior to randomization;
• A corrected QT (Fridericia) \> 500 msec or history of prolonged QT syndrome;
• Use of products containing alcohol, caffeine, xanthine, or ephedrine within 48 hours before dosing;

Sponsors & Collaborators

• Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.): lead
• Universitätsklinikum Köln: collaborator
• Innovative Medicines Initiative: collaborator

Study Sites (1)

University Hospital Cologne-Clinical Trial Center

Cologne, 50931, Germany

Location

MeSH Terms

Conditions

Acute Kidney Injury; Renal Insufficiency, Chronic; Bacterial Infections

Interventions

Minocycline; WW Domain-Containing Oxidoreductase

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Early Termination of the study lead to a small number of subjects analyzed.

Results Point of Contact

• Title: Global Health Science Center
• Organization: Melinta Therapeutics

medinfo@melinta.com

1-844-633-6568

Study Officials

• Oliver Cornely, MD

  Universitätsklinikum Köln

  STUDY DIRECTOR

• Volker Burst, MD, PD

  Universitätsklinikum Köln

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 21, 2016
• Study Start: May 29, 2017
• Primary Completion: June 4, 2018
• Study Completion: June 4, 2018
• Last Updated: September 4, 2019
• Results First Posted: July 24, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)