A SAD and MAD Study of the Safety, Tolerability, and Pharmacokinetics of ATH-1105

ATH-1105 a Phase 1, Double-Blind, Placebo-Controlled, Single-and-Multiple-Oral-Dose, Safety, Tolerability, and Pharmacokinetic Study in Healthy Male and Female Subjects

The goal of this Phase 1 interventional study is to assess the safety, tolerability and pharmacokinetics of ATH-1105 in healthy male and female participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ATH-1105; Drug: Placebo

Detailed Description

The study is a Phase 1, First-In-Human study consisting of two parts (A and B). Part A will comprise a single-dose, double-blind, placebo-controlled, sequential-group design. Part B will comprise a multiple-dose, placebo-controlled, sequential-group design.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Fortrea Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index between 18.0 and 32.0 kg/m2 inclusive.
• In good health, determined by no clinically significant findings from medical history, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations at screening and check-in or predose on Day 1
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Exclusion Criteria:

Medical Conditions:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs

• Any of the following:

  1. QTcF >450 ms in males or >470 ms in females
  2. QRS duration >110 ms
  3. PR interval >220 ms
  4. Findings which would make QTc measurements difficult or QTc data uninterpretable.
  5. History of additional risk factors for torsades de pointes
• Confirmed systolic blood pressure >140 or <90 mmHg, diastolic blood pressure >90 or <50 mmHg, and pulse rate >100 or <40 beats per minute.
• Positive hepatitis panel and/or positive human immunodeficiency virus test
• Part B only: Current psychiatric disorder, suicidal ideation in the previous 2 years (as assessed by the Columbia-Suicide Severity Rating Scale [C-SSRS]), or a lifetime suicide attempt.

Prior/concomitant therapy:

• Administration of any vaccine in the 30 days prior to dosing.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes
• Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing
• Use or intend to use slow-release medications/products considered to still be active within 14 days prior to check-in
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to check-in

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATH-1105; Part A: ATH-1105 administered once as an oral solution. Part B: ATH-1105 administered once daily as an oral solution for 10 days.	Drug: ATH-1105; ATH-1105 in oral form. Participants will be administered ATH-1105 once in Part A and once daily for 10 days in Part B.
Placebo Comparator: Placebo; Part A: Placebo administered once as an oral solution Part B: Placebo administered once daily as an oral solution	Drug: Placebo; Placebo in oral form. Participants will be administered Placebo once in Part A and once daily for 10 days in Part B.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety and tolerability of single or multiple ascending doses of ATH-1105 as measured by incidence of AEs, determined by clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead ECG	Part A: Up to 7 days post-dose, Part B: Up to 7 days post final dose on day 10
Severity of Treatment-Emergent Adverse Events	Treatment-emergent adverse events will be graded on a 1 through 5 scale, based on severity as determined by the principal investigator.	Part A: Up to 7 days post-dose, Part B: Up to 7 days post final dose on day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration time curve (AUC)	AUC will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.	Part A: Up to 48 hours post-dose, Part B: Up to 48 hours post final dose on Day 10
Maximum observed plasma concentration (Cmax)	Cmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.	Part A: Up to 48 hours post-dose, Part B: Up to 48 hours post final dose on Day 10
Time to maximum observed plasma concentration (Tmax)	Tmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.	Part A: Up to 48 hours post-dose, Part B: Up to 48 hours post final dose on Day 10
Half-life (t1/2)	t1/2 will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.	Part A: Up to 48 hours post-dose, Part B: Up to 48 hours post final dose on Day 10
Amount of IMP excreted unchanged in the urine (Ae)	Amount of IMP excreted unchanged in the urine will be determined from all collected urine samples from baseline through up to 48 hours post-dose	Part A: Up to 48 hours post-dose, Part B: Up to 48 hours post final dose on Day 10
IMP Concentration in Cerebrospinal Fluid	Amount of IMP in the urine will be determined from all collected CSF samples from baseline through up to 48 hours post-dose	Will occur at calculated maximum plasma concentration.
Accumulation Ratio (AUC) of IMP in Urine	Accumulation Ratio in urine will be determined from all collected urine samples from baseline through up to 48 hours post-dose	Part A: Up to 48 hours post-dose, Part B: Up to 48 hours post final dose on Day 10
Accumulation Ratio (AUC) of IMP in Plasma	Accumulation Ratio in plasma will be determined from all collected plasma samples from baseline through up to 48 hours post-dose	Part A: Up to 48 hours post-dose, Part B: Up to 48 hours post final dose on Day 10

Collaborators and Investigators

• Sponsor: Athira Pharma
• Collaborators: Fortrea Holdings, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Actual): November 25, 2024
• Study Completion (Actual): November 25, 2024

Study Registration Dates

• First Submitted: May 17, 2024
• First Submitted That Met QC Criteria: May 22, 2024
• First Posted (Actual): May 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: ATH-1105
• Other Study ID Numbers: ATH-1105-0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No