Single Dose Escalation Study of P1101 in Healthy Adult Male Subjects

Phase I, Randomized Double-Blind, Active Control, Single Dose Escalation Study of P1101 in Healthy Adult Male Subjects

This was a single-center, double-blind, randomized, active control, single dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of P1101 in 48 healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: P1101 (24 mcg); Drug: P1101 (48 mcg); Drug: P1101 (90 mcg); Drug: P1101 (180 mcg); Drug: P1101 (225 mcg); Drug: P1101 (270 mcg); Drug: Pegasys

Detailed Description

The primary objectives were to determine the safety and tolerability of single ascending subcutaneous doses of P1101 and to determine the pharmacokinetics of P1101 in single ascending subcutaneous doses of P1101 in healthy male subjects.

The secondary objectives were to evaluate the occurrence of side effects in healthy subjects receiving either P1101 or PEGASYS; to compare the pharmacokinetic parameters for P1101 and PEGASYS; and to assess the effect of P1101 on the biomarkers 2',5' oligoadenylate synthetase and neopterin.

A total of 48 subjects were enrolled to receive subcutaneous injection of P1101 in the dose level of 24 , 48 , 90 , 180 , 225 , or 270 mcg or to receive subcutaneous injection of 180 mcg Pegasys.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada
    • Anapharm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Main Inclusion Criteria:

1. Be healthy males, non-smokers, ≥18 and ≤45 years of age;
2. Able to attend all scheduled visits and to comply with all study procedures.

Main Exclusion Criteria:

1. Clinically significant illness or surgery within 4 weeks prior to dosing;
2. Any clinically significant abnormality or abnormal laboratory test results found during screening;
3. Positive test for hepatitis B, hepatitis C, or HIV at screening;
4. Clinically significant vital sign abnormalities at screening;
5. History of significant alcohol or drug abuse within one year prior to the screening visit;
6. History of severe allergic or hypersensitivity reactions;
7. Use of an investigational drug or participation in an investigational drug trial within the last 4 weeks;
8. Any clinically significant history or presence of neurological, cardiovascular, pulmonary, hematological, immunologic, metabolic or other uncontrolled systemic disease;
9. Clinically significant history or known presence of psychiatric disorders, including but not limited to depression, anxiety, and sleep disorders;
10. Body organ transplant and are taking immunosuppressants;
11. History of malignant disease;
12. History or presence of endocrine disorders;
13. History of coagulation disorders and blood dyscrasias;
14. Inability to comprehend the written consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: P1101 24 mcg; A total of 6 subjects received single dose of 24 mcg P1101	Drug: P1101 (24 mcg); P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 24 mcg subcutaneously.
EXPERIMENTAL: P1101 48 mcg; A total of 6 subjects received single dose of 48 mcg P1101	Drug: P1101 (48 mcg); P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 48 mcg subcutaneously.
EXPERIMENTAL: P1101 90 mcg; A total of 6 subjects received single dose of 90 mcg P1101	Drug: P1101 (90 mcg); P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 90 mcg subcutaneously.
EXPERIMENTAL: P1101 180 mcg; A total of 6 subjects received single dose of 180 mcg P1101	Drug: P1101 (180 mcg); P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 180 mcg subcutaneously.
EXPERIMENTAL: P1101 225 mcg; A total of 6 subjects received single dose of 225 mcg P1101	Drug: P1101 (225 mcg); P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 225 mcg subcutaneously.
EXPERIMENTAL: P1101 270 mcg; A total of 6 subjects received single dose of 270 mcg P1101	Drug: P1101 (270 mcg); P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 270 mcg subcutaneously.
ACTIVE_COMPARATOR: Pegasys 180 mcg; A total of 12 subjects received single dose of 180 mcg Pegasys	Drug: Pegasys; Pegasys for injection, 180 mcg/mL, 1.0 mL/vial, Dose/subject: 180 mcg subcutaneously.; Other Names: peginterferon alfa-2a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event	Frequency and severity of all adverse events among subjects, including frequency and severity of drug-related adverse events.	Through study Day 35
AUC of P1101 and Pegasys	Area under the serum concentration-time curve from time 0 to infinity	Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
AUC0-t of P1101 and Pegasys	Area under the serum concentration-time curve from time zero to the last measurable concentration (AUC0-t)	Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
Cmax of P1101 and Pegasys	Maximum serum concentration; the highest concentration observed during a dosage interval.	Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
Ct of P1101 and Pegasys	The last measured serum concentration, the last concentration above the lower limit of quantification following dose	Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
Tmax of P1101 and Pegasys	The time that Cmax was observed	Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
T½ of P1101 and Pegasys	Terminal elimination half-life	Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
λz (Ke) of P1101 and Pegasys	The terminal elimination rate constant; calculated using linear regression on the terminal portion of the Ln-concentration versus time curve	Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2',5' oligoadenylate synthetase (OAS): Emax	Maximum serum biomarker response; the highest biomarker concentration observed during a dosage interval.	Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
2',5' oligoadenylate synthetase (OAS): Tmax	The time that Emax was observed.	Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
2',5' oligoadenylate synthetase (OAS): AUC0-t	Area under the biomarker concentration versus time curve from time 0 to the last measured concentration.	Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
Neopterin: Emax	Maximum serum biomarker response; the highest biomarker concentration observed during a dosage interval.	Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
Neopterin: Tmax	The time that Emax was observed.	Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
Neopterin: AUC0-t	Area under the biomarker concentration versus time curve from time 0 to the last measured concentration.	Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Analysis of the concentration of anti-P1101 antibody.	Samples were collected within 1 hour pre-dose, at 336 and 672 hours after dose administration

Collaborators and Investigators

• Sponsor: PharmaEssentia
• Investigators: Principal Investigator: Richard Larouche, MD, Anapharm 5160, boul. Décarie, suite 800 Montréal, Québec, Canada, H3X 2H9

Publications and helpful links

General Publications

• Huang YW, Qin A, Fang J, Wang TF, Tsai CW, Lin KC, Teng CL, Larouche R. Novel long-acting ropeginterferon alfa-2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial. Br J Clin Pharmacol. 2022 May;88(5):2396-2407. doi: 10.1111/bcp.15176. Epub 2021 Dec 28.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 7, 2009
• Primary Completion (ACTUAL): June 26, 2010
• Study Completion (ACTUAL): June 26, 2010

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (ACTUAL): November 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: P1101, phase 1, healthy volunteers
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2a
• Other Study ID Numbers: A09-102

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