A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MA-0211 in Healthy Adult Subjects Including a Food Effect Cohort

NCT03682484 | Completed Phase 1 FDA Drug

• 1 other identifier: 0367-CL-0001
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

This first-in-human (FiH) study consists of 2 parts: single ascending dose (SAD) with evaluation of food effect (Part 1) and multiple ascending dose (MAD) (Part 2). The primary purpose of this study is to evaluate the safety and tolerability of single ascending oral doses in Part 1 (SAD Including Evaluation of Food Effect) and multiple ascending oral doses in Part 2 (MAD) of MA-0211 in healthy adult participants. This study will also evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending and multiple ascending oral doses of MA-0211 in healthy adult participants. In addition, this study will evaluate the effect of a single oral dose of MA-0211 on the QT interval using Fridericia's Correction (QTcF); determine the effect of food on the PK of a single oral dose of MA-0211 as well as evaluate the effect of multiple oral doses of MA-0211 on the QTcF.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetics; MA-0211; Single Ascending Dose; Healthy Volunteer; Multiple Ascending Dose; Pharmacodynamics

Outcome Measures

Primary Outcomes (6)

• Safety and tolerability assessed by nature, frequency, and severity of Adverse Events (AEs)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

  Up to day 26

• Number of participants with vital sign abnormalities and /or adverse events (AEs)

  Number of participants with potentially clinically significant vital sign values.

  Up to day 26

• Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant laboratory values.

  Up to day 26

• Safety assessed by routine 12- lead electrocardiogram (ECG)

  The overall conclusion of the routine ECG will be recorded as normal, abnormal not clinically significant, or abnormal clinically significant.

  Up to day 26

• Safety assessed by continuous 12- lead electrocardiogram (ECG)

  The overall conclusion of the continuous ECG will be recorded as normal or abnormal, with a comment added if abnormal.

  Up to day 15

• Safety assessed by Real-time cardiac monitoring (telemetry) (Part 1)

  Number of participants with potentially clinically significant telemetry abnormalities.

  Day 1

Secondary Outcomes (25)

• Part 1: Pharmacokinetics (PK) of MA-0211 in plasma: area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)

  Up to day 6

• Part 1: PK of MA-0211 in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)

  Up to day 6

• Part 1: PK of MA-0211 in plasma: percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf(%extrap))

  Up to day 6

• Part 1: PK of MA-0211 in plasma: maximum concentration (Cmax)

  Up to day 6

• Part 2 (Only First Dose and Last Dose): PK of MA-0211 in plasma: maximum concentration (Cmax)

  Up to day 19

Study Arms (5)

MA-0211 Single Ascending Dose (fasting conditions)

EXPERIMENTAL

Successive cohorts of 8 participants (1-7 cohorts) will be started on a fixed single dose of MA-0211 or matching Placebo under fasting conditions. The first two participants will receive either MA-0211 or matching placebo. If no safety issues are observed in the first 24 hours in the first two participants, then the remaining six participants will be dosed.

Drug: MA-0211

Placebo Single Ascending Dose (fasting conditions)

PLACEBO COMPARATOR

Successive cohorts of 8 participants (1-7 cohorts) will be started on a fixed single dose of MA-0211 or matching Placebo under fasting conditions. The first two participants will receive either MA-0211 or matching placebo. If no safety issues are observed in the first 24 hours in the first two participants, then the remaining six participants will be dosed.

Drug: Placebo

MA-0211 Single Ascending Dose (food effect)

EXPERIMENTAL

A single cohort of 8 participants will be started on a fixed single dose of MA-0211, within 30 minutes after the start and 5 minutes after the completion of an US Food and Drug Administration (FDA) high fat breakfast.

Drug: MA-0211

MA-0211 Multiple Ascending Dose

EXPERIMENTAL

Successive cohorts of 12 participants (1-3 cohorts) will receive oral doses of MA-0211 or matching Placebo for 14 days.

Drug: MA-0211

Placebo Multiple Ascending Dose

PLACEBO COMPARATOR

Successive cohorts of 12 participants (1-3 cohorts) will receive oral doses of MA-0211 or matching Placebo for 14 days.

Drug: Placebo

Interventions

MA-0211 DRUG

oral

Also known as: ASP0367

MA-0211 Multiple Ascending Dose; MA-0211 Single Ascending Dose (fasting conditions); MA-0211 Single Ascending Dose (food effect)

Placebo DRUG

oral

Placebo Multiple Ascending Dose; Placebo Single Ascending Dose (fasting conditions)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has a body mass index (BMI) range of 18.5 to 32.0 kg/m2, inclusive, and weighs at least 50 kg at screening.
• Female subject must either:
• Be of nonchildbearing potential: Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy)
• Or, if of childbearing potential, agree not to try to become pregnant during the study and for 28 days after the final study drug administration, and have a negative blood/urine pregnancy test at screening and day -2, and if heterosexually active, agree to consistently use 1 form of highly effective birth control starting at screening and throughout the study period and for 28 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 28 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration.
• A sexually active male subject with female partner(s) who are of childbearing potential is eligible if:
• Agree to use a male condom starting at screening and continue throughout study treatment and for 90 days after the final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below the subject's female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continue throughout study treatment and for 90 days after the final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the study period, and for 90 days after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 28 days after the final study drug administration.
• Subject agrees not to participate in another interventional study while participating in the present clinical study, defined as signing the informed consent form until completion of the last study visit.

You may not qualify if:

• Subject participated in any clinical study or has been treated with any investigational drugs within 28 days prior to screening.
• Subject has any condition which makes the subject unsuitable for clinical study participation.
• Female subject who has been pregnant within 6 months prior to screening assessment or breast feeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to MA-0211, or any components of the formulation used.
• Subject has had previous exposure with MA-0211.
• Subject has any of the liver function tests (aspartate aminotransferase \[AST\], alanine amino-transferase \[ALT\], alkaline phosphatase \[ALP\], gamma-glutamyl transferase \[GGT\] and total bilirubin \[TBL\]) above the upper limit of normal at day -2. In such a case, the assessment may be repeated once.
• Subject has total creatine kinase greater than 1.5 times the upper limit of normal or troponin I above the upper limit of normal at day -2.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to study drug administration.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, psychiatric, dermatologic, renal and/or other major disease or malignancy.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to (day -2).
• Subject has any clinically significant abnormality following the investigator's review of the physical examination, ECG and protocol-defined clinical safety laboratory tests at screening or day 2.
• Subject has a mean heart rate \< 45 or \> 90 beats per minute; mean Systolic blood pressure (SBP) \> 140 mmHg; mean diastolic blood pressure (DBP) \> 90 mmHg at day -2 (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; heart rate will be measured automatically). If the mean heart rate, SBP or DBP exceeds the limits above, 1 additional triplicate can be taken (day -2).
• Subject has a mean QT interval using Fridericia's correction (QTcF) \> 430ms (for males) and \>450ms (for females) at day 2 or if the subject has any family history of long QT syndrome (LQTS). If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken (day -2).
• Subject has used any prescribed or nonprescribed drugs (including vitamins, calcium and iron supplements, natural and herbal remedies \[e.g., St. John's Wort\]) in the 2 weeks (or 5 elimination half-lives, whichever is longer) prior to study drug administration, except for occasional use of acetaminophen (up to 2 g/day \[prn\]). In addition, subject has used any peroxisome proliferator-activated receptor (PPAR) ligands such as fibrates and thiazolidinediones in the 4 weeks prior to day -2.
• Subject has smoked or has used tobacco-containing products and nicotine or nicotine containing products in the past 6 months prior to screening.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (1)

Parexel - Baltimore

Baltimore, Maryland, 21225, United States

Location

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2018
• First Posted: September 24, 2018
• Study Start: June 29, 2017
• Primary Completion: March 26, 2018
• Study Completion: March 26, 2018
• Last Updated: October 16, 2024

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)