Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PN-881 in Healthy Subjects.

Not Applicable

Not yet recruiting

• Conditions: Healthy Volunteer
• Interventions: Drug: PN-881 Oral Solution; Drug: Placebo; Drug: PN-881 Oral Tablet

• Registration Number: NCT07153146
• Lead Sponsor: Protagonist Therapeutics, Inc.

Brief Summary

The goal of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PN-881 in healthy adult participants.

Detailed Description

PN-881 will be administered in oral solution and tablet formulations, with dosing under fasting or fed conditions depending on the study part.

The study consists of five parts:

Part 1 - Single Ascending Dose (SAD): Randomised, double-blind, placebo-controlled Part 2 - Multiple Ascending Dose (MAD): Randomised, double-blind, placebo-controlled Part 3 - Tablet Formulation Comparison: Open-label, crossover design; participants will receive different oral tablet formulations Part 4 - Effect of Food: Open-label, crossover design to assess the effect of food on the pharmacokinetics of PN-881. Participants will receive PN-881 tablet formulations in fasted and fed conditions.

Part 5 - Dosing Frequency Comparison: Open-label, randomized study comparing once-daily and twice-daily dosing.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-22
• Study First Submitted QC: 2025-08-25
• Last Update Submitted: 2025-08-25
• Study First Posted: 2025-09-03
• Last Update Posted: 2025-09-03
• Study Start: 2025-09-08
• Primary Completion: 2026-06-15
• Study Completion: 2026-06-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

1. Healthy male and female participants of non-childbearing potential, aged 18-65 years inclusive
2. Body mass index (BMI) between 18 and 32 kg/m² (inclusive) at screening
3. Willing and able to comply with all study requirements and provide written informed consent
4. Male participants with female partners of childbearing potential must agree to use highly effective contraception during the study and for 90 days after the last dose

Exclusion Criteria

1. Clinically significant history or presence of cardiovascular, gastrointestinal, hepatic, renal, neurological, psychiatric, or allergic diseases
2. History of neoplastic disease (except adequately treated non-melanoma skin cancer)
3. Positive test for hepatitis B, hepatitis C, or HIV at screening
4. History of substance abuse or recreational IV drug use within the past 2 years
5. Clinically significant infection or fever (>38°C) within 2 weeks prior to screening
6. Use of any prescription/non-prescription drugs or herbal supplements within 7 days or 5 half-lives before dosing (unless approved by investigator)
7. Supine blood pressure or ECG abnormalities outside protocol-defined ranges
8. Use of tobacco/nicotine products exceeding 5 cigarettes/day or 2 chews/day
9. Consumption of >21 alcohol units/week (males) or >14 units/week (females)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PN-881 Oral Solution Single Ascending Dose	PN-881 Oral Solution	PN-881 Oral Solution Single Ascending Dose
Placebo Oral Solution Single Ascending Dose	Placebo	Placebo single ascending doses
PN-881 Oral Solution Multiple Ascending Dose	PN-881 Oral Solution	PN-881 Multiple Ascending Doses
Placebo Oral Solution Multiple Ascending Dose	Placebo	Placebo, multiple ascending doses
PN-881 Oral Tablet Single Dose	PN-881 Oral Tablet	PN-881 oral tablet single dose
PN-881 Oral Tablet Multiple Dose	PN-881 Oral Tablet	PN-881 oral tablet multiple dose

Primary Outcome Measures

Name	Time	Method
Incidence and severity of treatment-emergent adverse events (TEAEs)	Predose to 7 days after last dose	Evaluate the safety and tolerability of PN-881 in comparison to placebo after single and multiple doses in healthy subjects assessed for severity, seriousness, and relation to the investigational product.

Secondary Outcome Measures

Name	Time	Method
Maximum observed plasma concentration (Cmax) of PN-881	48 hours following the first dose and the last dose	Highest measured plasma concentration of PN-881 following oral administration.
Area under the plasma concentration-time curve (AUC) of PN-881	Predose to 48 hrs after the first and last dose.	AUC calculated from 0 to infinity.
Levels of biomarker in serum	Day 1 Predose up to 48 hrs post (last) dose	Pharmacodynamics (PD) of PN-881 by means of increase in levels of biomarker by PN-881 after single and multiple oral doses.

Trial Locations

Locations (1)

Nucleus Network; 🇦🇺 Melbourne, Victoria, Australia