Dysautonomia International

A Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD3974 in Healthy Participants

Purpose

The purpose of this study is to assess the safety and tolerability of AZD3974 and characterize the pharmacokinetics (PK) of AZD3974 following oral administration to healthy participants, including participants of Japanese and Chinese descent.

Condition

Healthy Participants

Eligibility

Eligible Ages: Between 18 Years and 55 Years
Eligible Sex: All
Accepts Healthy Volunteers: Yes

Inclusion Criteria

Healthy male and female (of non-childbearing potential) participants with suitable veins for cannulation or repeated venipuncture at the Screening Visit. - All females must have a negative pregnancy test. Females of non-childbearing potential must be confirmed via post-menopausal status or documentation of irreversible surgical sterilization at the Screening Visit. - Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods. - Have a body mass index between 18 and 32 kg/m2 inclusive and weigh at least 50 kg at Screening. - For healthy Japanese cohorts (Part A2 and Part B2): healthy male and female participants are to be Japanese (eg, natives of Japan or Japan Americans), defined as having both parents and 4 grandparents who are Japanese. This includes second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan. - For healthy Chinese cohort (Part A3): healthy male and female Chinese participants for whom both parents and 4 grandparents are Chinese. This includes second and third generation participants of Chinese descent whose parents or grandparents are living in a country other than China.

Exclusion Criteria

History of any clinically important disease or disorder which, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. - History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. - Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention. - Any abnormal laboratory values, vital signs, or any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results. - Any positive result on Screening for serum hepatitis B and C viruses and human immunodeficiency virus. - Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12 lead electrocardiography at Screening and/or admission to the Clinical Unit . - Known or suspected history of alcohol or drug abuse or excessive intake of alcohol. - Positive screen for drugs of abuse, or alcohol, or cotinine. - History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity. - Participants who have previously received AZD3974.

Study Design

Phase: Phase 1
Study Type: Interventional
Allocation: Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: Single (Participant)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Part A1 (SAD) Cohort 1: AZD3974 (Dose 1)	Healthy participants will receive a single dose of AZD3974 - Dose 1	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A1 (SAD) Cohort 2: AZD3974 (Dose 2)	Healthy participants will receive a single dose of AZD3974 - Dose 2	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A1 (SAD) Cohort 3: AZD3974 (Dose 3) (Food Effect Cohort)	Healthy participants will receive two single doses of AZD3974 - Dose 3	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A1 (SAD) Cohort 4: AZD3974 (Dose 4)	Healthy participants will receive a single dose of AZD3974 - Dose 4	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A1 (SAD) Cohort 5: AZD3974 (Dose 5)	Healthy participants will receive a single dose of AZD3974 - Dose 5	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A1 (SAD) Cohort 6: AZD3974 (Dose 6)	Healthy participants will receive a single dose of AZD3974 - Dose 6	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A1 (SAD) optional additional Cohort 7: AZD3974	Healthy participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A1 (SAD) optional additional Cohort 8: AZD3974	Healthy participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Placebo Comparator Part A1 (SAD) Cohort: Placebo	Healthy participants will receive a single dose of matching placebo to AZD3974	Other: Placebo Placebo will be administered as an oral solution.
Placebo Comparator Part A1 (SAD) Cohort 3: Placebo (Food Effect Cohort)	Healthy participants will receive two single doses of matching placebo to AZD3974	Other: Placebo Placebo will be administered as an oral solution.
Experimental Part A2 (SAD) Japanese Cohort 1: AZD3974	Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A2 (SAD) Japanese Cohort 2: AZD3974	Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A2 (SAD) Japanese Cohort 3: AZD3974	Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A2 (SAD) optional additional Japanese Cohort 4: AZD3974	Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Placebo Comparator Part A2 (SAD) Japanese Cohort: Placebo	Healthy Japanese participants will receive a single dose of matching placebo to AZD3974	Other: Placebo Placebo will be administered as an oral solution.
Experimental Part A3 (SAD) Chinese Cohort 1: AZD3974	Healthy Chinese participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part A3 (SAD) optional additional Chinese Cohort 2: AZD3974	Healthy Chinese participants will receive a single dose of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Placebo Comparator Part A3 (SAD) Chinese Cohort: Placebo	Healthy Chinese participants will receive a single dose of matching placebo to AZD3974	Other: Placebo Placebo will be administered as an oral solution.
Experimental Part B1 (MAD) Cohort 1: AZD3974	Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part B1 (MAD) Cohort 2: AZD3974	Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part B1 (MAD) Cohort 3: AZD3974	Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part B1 (MAD) Cohort 4: AZD3974	Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part B1 (MAD) optional additional Cohort 5: AZD3974	Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part B1 (MAD) optional additional Cohort 6: AZD3974	Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Placebo Comparator Part Bl (MAD) Cohort: Placebo	Healthy participants will receive multiple doses of matching placebo to AZD3974	Other: Placebo Placebo will be administered as an oral solution.
Experimental Part B2 (MAD) Japanese Cohort 1: AZD3974	Healthy Japanese participants will receive multiple doses of AZD397	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Experimental Part B2 (MAD) optional additional Japanese Cohort 2: AZD3974	Healthy Japanese participants will receive multiple doses of matching placebo to AZD3974	Drug: AZD3974 AZD3974 will be administered as an oral solution.
Placebo Comparator Part B2 (MAD) Japanese Cohort: Placebo	Healthy Japanese participants will receive multiple doses of matching placebo to AZD3974	Other: Placebo Placebo will be administered as an oral solution.

Recruiting Locations

Research Site
Baltimore, Maryland 21225

More Details

Status: Recruiting
Sponsor: AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

This is a first in human, randomized, single-blind, placebo-controlled study. It consists of two parts. Part A (single ascending dose - SAD): This study part will enroll six cohorts (plus two optional additional cohorts) of healthy participants (Part A1), three cohorts (plus one optional additional cohort) of healthy Japanese participants (Part A2) and one cohort (plus one optional additional cohort) of healthy Chinese participants (Part A3). Cohort 3 of Part A1 will be extended to evaluate the effect of food intake on the PK of AZD3974. In Part A (all cohorts), participants will receive a single dose of AZD3974 or placebo. Part B (Multiple Ascending Dose - MAD): This study part will consist of four cohorts (plus two optional additional cohorts) of healthy participants (Part B1) and one cohort (plus one optional additional cohort) of healthy Japanese participants (Part B2). In all Part B cohorts, participants will receive multiple doses of AZD3974 or placebo. Both Part A and Part B will comprise of: - A Screening Period of maximum 28 days - A Dosing session during which participants will receive the study intervention at study specific time points. - Follow-up Period of 7 days post last-dose.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.