Pharmacokinetics and Pharmacodynamics of Different PTG-300 Regimens in Healthy Volunteers

An Open-label Crossover Study Evaluating the Pharmacokinetics and Pharmacodynamics of Different PTG-300 Regimens in Healthy Volunteers

To estimate the bioavailability of PTG-300 following subcutaneous and intramuscular administration in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: PTG-300

Detailed Description

This is a single center, open-label study in healthy males. Subjects will be screened for eligibility within 28 days of dosing.

Twelve subjects will receive single doses of the following treatments in a fixed sequence:

Treatment A: Intravenous injection of 1.5 mg PTG-300. Treatment B: 40 mg (40 mg/mL) PTG-300 administered subcutaneously. Treatment C: 40 mg (200 mg/mL) PTG-300 administered subcutaneously. Treatment D: 40 mg (40 mg/mL) PTG-300 administered intramuscularly.

There will be a washout period of at least 7 days between Treatment A and Treatment B and at least 12 days between Treatments B, C, and D.

Subjects' safety will be monitored, and blood samples will be collected for pharmacokinetics and pharmacodynamics (serum iron, serum ferritin, serum transferrin, and transferrin saturation [TSAT]).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Protagonist Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male volunteers, age 18 to 65 years, inclusive.
2. Subjects must have a Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive.
3. Subjects must have clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator.
4. Agree to use a barrier method of contraception from Day -2 to 90 days after the last dose of study drug.
5. Subjects must have the ability and willingness to attend the necessary visits to the study center.

Exclusion Criteria:

1. History of clinically significant endocrine, neurological, gastrointestinal, cardiovascular, haematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.
2. History of malignancy, with the exception of adequately treated non-melanomatous skin carcinoma.
3. Mentally or legally incapacitated, has significant emotional problems at the time of Screening Visit or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder that would impact the subjects ability to participate in the trial according to the Investigator.
4. Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to screening; evidence of intestinal infection within 30 days prior to screening.
5. History of severe allergic or anaphylactic reactions.
6. A supine blood pressure outside the range of 90 to 139 mm Hg systolic and 50 to 89 mm Hg diastolic, OR heart rate (HR) >100 beats per minute at Screening and at Day -1.
7. Laboratory values that are outside the normal range and considered clinically significant by the Investigator.
8. Positive test for hepatitis C antibody, hepatitis B surface antigen or human immunodeficiency virus (HIV) antibody at Screening.
9. Subjects considered at high risk of iron deficiency according to the Investigator.
10. Subjects with iron deficiency as defined by a ferritin or transferrin saturation below the normal range
11. Clinically significant abnormality on ECG performed at the Screening Visit or prior to administration of the initial dose of study drug.
12. Corrected QT (QTcF) greater than 450 msec at Screening.
13. Subjects with a positive toxicology screening panel.
14. Subjects with a history of substance abuse or dependency or history of recreational IV drug use (by self-declaration).
15. Consumption of >14 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit, or a 125 mL glass of wine).
16. Unable to refrain from or anticipates the use of any medications, including prescription and non-prescription drugs and herbal remedies (such as St. John's Wort [Hypericum perforatum]), beginning 14 days (or 5 half lives, whichever is longer) before administration of the initial dose of study drug and continuing throughout the study until the final study visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous; PTG-300 Intravenous	Drug: PTG-300; Active drug
Experimental: Subcutaneous Low Concentration; PTG-300 Subcutaneous Low Concentration	Drug: PTG-300; Active drug
Experimental: Subcutaneous High Concentration; PTG-300 Subcutaneous High Concentration	Drug: PTG-300; Active drug
Experimental: Intramuscular; PTG-300 Intramuscular	Drug: PTG-300; Active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioavailability of PTG-300	Bioavailability (area under the plasma-concentration time) of PTG-300 following subcutaneous and intramuscular administration in healthy volunteers	Week 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Iron Pharmacodynamics of PTG-300	Change from baseline in serum iron following subcutaneous and intramuscular administration in healthy volunteers	Week 1
TSAT Pharmacodynamics of PTG-300	Change from baseline in transferrin saturation (TSAT) following subcutaneous and intramuscular administration in healthy volunteers	Week 1

Collaborators and Investigators

• Sponsor: Protagonist Therapeutics, Inc.
• Investigators: Study Director: Study Director, Protagonist Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): January 12, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: August 10, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: PTG-300-07

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No