A Study to Find a Suitable Dose of ASP8731 and Check for Medical Problems at Each Dose in Healthy Adults

NCT05167526 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 8731-CL-0101
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

ASP8731 is a potential new treatment for people with sickle cell disease. Before ASP8731 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. They do this to find a suitable dose and to check for potential medical problems from the treatment. This type of study usually includes healthy adults but can include people with the relevant condition. The main aim of this study is to learn if healthy adults have any medical problems after taking different doses of ASP8731. This study will be in 2 parts. In Part 1, different small groups of people will take lower to higher doses of ASP8731 or a placebo. In this study a placebo looks like ASP8731 but will not have any medicine in it. This is done to find suitable doses of ASP8731 and work out how often it should be taken. Some of this information will be used in Part 2 of the study. The first group will take the lowest dose of ASP8731 or the placebo. A medical expert panel will check the results from this group and decide which ASP8731 dose the next group can take. The panel will do this for each group until all groups have taken ASP8731 or until a suitable dose of ASP8731 has been reached. In Part 1, people will visit the study clinic 4 times. The first visit is to check if they can take part. People will be asked about their medical history, have a physical exam, and their vital signs checked (pulse rate, temperature, and blood pressure). Also, they will have an ECG to check their heart rhythm and have some blood samples taken for laboratory tests. For women this will include a pregnancy test. At the second visit, people will stay in the study clinic for a few days. In most groups, people will be picked to take either ASP8731 or the placebo by chance alone. They will fast before taking ASP8731 or the placebo. 1 group will take ASP8731 with food. No-one in that group will take the placebo. After taking ASP8731 or the placebo (or just ASP8731 with food), people in all groups will give blood and urine samples during the next 3 days. Also, they will be checked for any medical problems during their clinic stay. People will return to the study clinic for a 2 follow-up visits - at about 8 and 30 days after they last took ASP8731 or the placebo. At these visits people will be asked if they have any medical problems. They will have a physical exam, have their vital signs checked (pulse rate, temperature, and blood pressure), and have some blood samples taken for laboratory tests. For women, this will include another pregnancy test. In Part 2, other different small groups of people will take lower to higher doses of ASP8731 or a placebo. How often it is taken will be worked out from Part 1.The first group will take the lowest dose of ASP8731 or the placebo each day over several days. A medical expert panel will check the results from this group and decide which ASP8731 dose the next group can take. The panel will do this for each group until all groups have taken ASP8731. In Part 2, people will visit the study clinic 5 times. The first visit is to check if they can take part. People will be asked about their medical history, have a physical exam, and their vital signs checked. Also, they will have an ECG and have some blood samples taken for laboratory tests. For women this will include a pregnancy test. At the second visit, people will stay in the study clinic for several days. In all groups, people will be picked to take either ASP8731 or the placebo by chance alone. After taking ASP8731 or the placebo, people in all groups will give blood samples throughout their stay. They will give urine samples during the last few days of their stay. Also, they will be checked for any medical problems during their clinic stay. After discharge, people will return to the clinic 4 days later for a third visit. At this visit, they will have some blood samples taken for laboratory tests. Also, they will have their vital signs checked and will be asked if they have any medical problems. People will return to the study clinic for a 2 follow-up visits - at about 15 and 30 days after they last took ASP8731 or the placebo. At these visits people will be asked if they have any medical problems. They will have a physical exam and have their vital signs checked. They will also have an ECG and have some blood samples taken for laboratory tests. For women, this will include another pregnancy test. No other visits are planned during this study.

Conditions

Healthy Participants

Keywords

Healthy Participants; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (8)

• Part 1: Safety and tolerability assessed by nature, frequency, and severity of Adverse Events (AEs)

  Adverse Events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study IP, whether or not considered related to the study investigational product (IP). 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 study IP. This includes events related to the comparator and events related to the (study) procedures.

  Up to Day 41

• Part 1: Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant laboratory values.

  Up to Day 41

• Part 1: 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 41

• Part 1: Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events

  Number of participants with potentially clinically significant ECG values.

  Up to Day 41

• Part 2: Safety and tolerability assessed by nature, frequency, and severity of Adverse Events (AEs)

  Adverse Events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study IP, whether or not considered related to the study investigational product (IP). 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 study IP. This includes events related to the comparator and events related to the (study) procedures.

  Up to Day 59

• Part 2: Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant laboratory values.

  Up to Day 59

• Part 2: 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 59

• Part 2: Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events

  Number of participants with potentially clinically significant ECG values.

  Up to Day 59

Secondary Outcomes (11)

• Part 1: Pharmacokinetics (PK) of ASP8731 in plasma: area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)

  Up to Day 7

• Part 1: PK of ASP8731 in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)

  Up to Day 7

• Part 1: PK of ASP8731 in plasma: maximum concentration (Cmax)

  Up to Day 7

• Part 2: First Dose PK of ASP8731 in plasma: area under the concentration-time curve from the time of dosing to 24 hours (AUC24)

  Up to Day 2

• Part 2: First Dose PK of ASP8731 in plasma: area under the concentration-time curve from the time of dosing to 12 hours (AUC12)

  Up to Day 2

Study Arms (6)

Part 1: ASP8731 Placebo

PLACEBO COMPARATOR

Participants receive a single dose of matching placebo under fasting conditions.

Drug: ASP8731 Matching Placebo

Part 1: ASP8731 3mg

EXPERIMENTAL

Participants receive a single dose of ASP8731 3mg under fasting conditions.

Drug: ASP8731

Part 1: ASP8731 12mg

EXPERIMENTAL

Participants receive a single dose of ASP8731 12 mg under fasting conditions.

Drug: ASP8731

Part 2: Placebo

PLACEBO COMPARATOR

Participants receive a multiple matching dose of placebo twice daily for 14 days under fasting conditions.

Drug: ASP8731 Matching Placebo

Part 2: ASP8731 6mg

EXPERIMENTAL

Participants receive ASP8731 6mg twice daily for 14 days under fasting conditions.

Drug: ASP8731

Part 1: ASP8731 6mg

EXPERIMENTAL

Participants receive a single dose of ASP8731 6 mg of under fasting conditions.

Drug: ASP8731

Interventions

ASP8731 DRUG

Oral

Part 1: ASP8731 12mg; Part 1: ASP8731 3mg; Part 1: ASP8731 6mg; Part 2: ASP8731 6mg

ASP8731 Matching Placebo DRUG

Oral

Part 1: ASP8731 Placebo; Part 2: Placebo

Eligibility Criteria

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

You may qualify if:

• Participant has a body mass index (BMI) range of 18.5 to 32.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Female participant is not pregnant and at least 1 of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final IP administration.
• Female participant must agree not to breastfeed starting at 90 days prior to screening and throughout the study period and for 30 days after final investigational product (IP) administration.
• Female participant must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.
• Male participant with female partner(s) of childbearing potential (including breastfeeding partner\[s\]) must agree to use contraception throughout the treatment period and for 90 days after final IP administration.
• Male participant must not donate sperm during the treatment period and for 90 days after final IP administration.
• Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration.
• Participant agrees not to participate in another interventional study while receiving study treatment in the present study.

You may not qualify if:

• Participant has received any investigational therapy within 28 days or 5 half lives, whichever is longer, prior to screening.
• Participant has any condition which makes the participant unsuitable for study participation.
• Participant has a known or suspected hypersensitivity to ASP8731 or any components of the formulation used.
• Female participant who has been pregnant within 6 months prior to screening or breastfeeding within 90 days prior to screening.
• Participant has had previous exposure with ASP8731.
• Participant has any of the liver function tests (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and total bilirubin) above the upper limit of normal (ULN) on day -1. In such a case, the assessment may be repeated once.
• Participant has any history of previously diagnosed Gilbert's syndrome.
• Participant has creatinine level outside normal limits on day -1. In such a case, the assessment may be repeated once.
• Participant has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to first IP administration.
• Participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic (e.g., sickle cell disease, hemoglobinopathies, hemolytic anemias, etc.), hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy.
• Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1.
• Participant has any clinically significant abnormality of the physical examination, ECG and protocol-defined clinical laboratory tests at screening or on day -1.
• Participant has a mean pulse \< 45 or \> 90 bpm; mean systolic blood pressure \> 140 mmHg; mean diastolic blood pressure \> 90 mmHg (measurements taken in triplicate after participant has been resting in the supine position for at least 5 minutes; pulse will be measured automatically) on day -1. If the mean blood pressure or pulse exceeds the limits above, 1 additional triplicate may be taken.
• Participant has a mean QT corrected for heart rate by Fridericia's cube root formula (QTcF) of \> 430 msec (for male participants) and \> 450 msec (for female participants) on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG may be taken.
• Participant has an abnormal heart rhythm such as prolonged QT interval, underlying heart disease, chronic kidney disease or receiving medicines which prolong the QT interval.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (1)

California Clinical Trials Medical Group

Glendale, California, 91206, United States

Location

Study Officials

• Medical Director Medical Specialties

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: December 22, 2021
• Study Start: March 7, 2022
• Primary Completion: November 10, 2022
• Study Completion: November 10, 2022
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)