A Phase 1 Study Investigating the Safety and Pharmacokinetics of Repeat-dose Intravenous Infusion of MTP-131 in Subjects With Impaired Renal Function

A Phase 1, 7 Day Repeat Dose, Parallel-Group, Open-Label Study to Evaluate the Safety and Pharmacokinetics of Intravenous Infusion of MTP-131 Administered in Subjects With Impaired Renal Function

This study is a Phase 1, open-label, parallel group, multiple dose study, in subjects over 18 years, to evaluate the safety, tolerability, and pharmacokinetics of one-hour intravenous infusion of MTP-131 administered for 7 consecutive days. Twenty-four subjects are planned to be enrolled into 4 cohorts of varying renal function, with each cohort consisting of 6 subjects.

Study Overview

• Status: Completed
• Conditions: Normal and Impaired Renal Function
• Intervention / Treatment: Drug: MTP-131; Drug: MTP-131; Drug: MTP-131; Drug: MTP-131

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Maimi, Florida, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is ≥18 years-of-age at the Screening Visit.
• Subject has signed an ICF before any study specific procedures are performed.

• Subjects selected for each cohort must satisfy the following creatinine clearance (CLCR) criteria (as determined by 24 hour urine collection and analysis):

  • Cohort 1 - Normal Renal Function, 24 hour CLCR ≥ 90 mL/min
  • Cohort 2 - Mild renal impairment, 24 hour CLCR ≥ 60-89 mL/min
  • Cohort 3 - Moderate renal impairment, 24 hour CLCR ≥ 30-59 mL/min
  • Cohort 4 - Severe renal impairment, 24 hour CLCR <30 not requiring dialysis
• Have a history of stable renal impairment as determined by standard estimated creatinine clearance methodology (at least 1 month within the same descriptive cohort) and be in a stable physical condition based on findings of medical history.

• Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until two months after the last dose of study drug:

  1. Abstinence, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use an acceptable method of contraception should they become sexually active.
  2. Maintenance of a monogamous relationship with a male partner who has been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit or confirmed via sperm analysis).
  3. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system.

Exclusion Criteria:

• Subject has history of any concurrent medical condition which, in the opinion of the investigator, significantly increases the potential risks associated with administration of MTP-131 or any other aspect of study participation, with the exception of renal impairment.
• Female subjects who are pregnant, planning to become pregnant, or lactating.
• Subject has history of cancer (with the exception of non-melanoma skin cancer), unless the subject has documentation of completed curative treatment
• Subject has history of renal transplantation.
• Subject has active inflammatory renal disease.
• Subject has a history of histamine intolerance (e.g., a known deficiency of endogenous or exogenous histamine degradation).
• Subject is currently receiving treatment with chemotherapeutic agents or immunosuppressant agents.
• Subject has positive serology for HIV 1, HIV 2, HBsAg or HCV.
• Subject has donated or received blood or blood products within the past 30 days.
• Subject participated in a clinical study involving investigational product within 30 days prior to the planned date of study drug administration.
• Subject has a history of clinically significant hypersensitivity or allergy to any of the excipients contained in the study drug.

• Subject has a history of active alcoholism or drug addiction during the year before the Screening Visit.

  • Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal renal function	Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with normal renal function.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with mild renal impairment.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with moderate renal impairment; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with severe renal impairment
Experimental: Mild renal impairment	Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with normal renal function.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with mild renal impairment.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with moderate renal impairment; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with severe renal impairment
Experimental: Moderate renal impairment	Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with normal renal function.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with mild renal impairment.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with moderate renal impairment; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with severe renal impairment
Experimental: Severe renal impairment	Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with normal renal function.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with mild renal impairment.; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with moderate renal impairment; Drug: MTP-131; MTP-131 administered as once-daily 1- hour intravenous infusion for 7 consecutive days in subjects with severe renal impairment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean peak plasma concentration (Cmax) of MTP-131 (ng/ml) in each cohort	Assessed up to Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events	Assessed up to Day 14

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: May 1, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: November 17, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Renal Impairment, Renal function, MTP-131, Bendavia™
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: SPICP-101