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

Protagonist Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: PN-881 Oral Tablet; Drug: PN-881 Oral Solution; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07153146

PN-881-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 142 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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142 participants in 6 patient groups, including a placebo group

PN-881 Oral Solution Single Ascending Dose

Experimental group

Description:

PN-881 Oral Solution Single Ascending Dose

Treatment:

Drug: PN-881 Oral Solution

Placebo Oral Solution Single Ascending Dose

Placebo Comparator group

Description:

Placebo single ascending doses

Treatment:

Drug: Placebo

PN-881 Oral Solution Multiple Ascending Dose

Experimental group

Description:

PN-881 Multiple Ascending Doses

Treatment:

Drug: PN-881 Oral Solution

Placebo Oral Solution Multiple Ascending Dose

Placebo Comparator group

Description:

Placebo, multiple ascending doses

Treatment:

Drug: Placebo

PN-881 Oral Tablet Single Dose

Experimental group

Description:

PN-881 oral tablet single dose

Treatment:

Drug: PN-881 Oral Tablet

PN-881 Oral Tablet Multiple Dose

Experimental group

Description:

PN-881 oral tablet multiple dose

Treatment:

Drug: PN-881 Oral Tablet