Single Dose Escalation Study of P1101 in Healthy Adult Male Subjects

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Be healthy males, non-smokers, ≥18 and ≤45 years of age; Able to attend all scheduled visits and to comply with all study procedures. Main Exclusion Criteria: Clinically significant illness or surgery within 4 weeks prior to dosing; Any clinically significant abnormality or abnormal laboratory test results found during screening; Positive test for hepatitis B, hepatitis C, or HIV at screening; Clinically significant vital sign abnormalities at screening; History of significant alcohol or drug abuse within one year prior to the screening visit; History of severe allergic or hypersensitivity reactions; Use of an investigational drug or participation in an investigational drug trial within the last 4 weeks; Any clinically significant history or presence of neurological, cardiovascular, pulmonary, hematological, immunologic, metabolic or other uncontrolled systemic disease; Clinically significant history or known presence of psychiatric disorders, including but not limited to depression, anxiety, and sleep disorders; Body organ transplant and are taking immunosuppressants; History of malignant disease; History or presence of endocrine disorders; History of coagulation disorders and blood dyscrasias; Inability to comprehend the written consent form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This was a single center, double-blind, randomized, active control, single dose escalation study, with P1101 (24, 48, 90, 180, 225, 270 mcg) as the test drug and Pegasys (180 ug) as the control drug.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P1101 24 mcg<br>A total of 6 subjects received single dose of 24 mcg P1101 | Drug: P1101 (24 mcg)<br>* P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 24 mcg subcutaneously.<br>|
| Experimental: P1101 48 mcg<br>A total of 6 subjects received single dose of 48 mcg P1101 | Drug: P1101 (48 mcg)<br>* P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 48 mcg subcutaneously.<br>|
| Experimental: P1101 90 mcg<br>A total of 6 subjects received single dose of 90 mcg P1101 | Drug: P1101 (90 mcg)<br>* P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 90 mcg subcutaneously.<br>|
| Experimental: P1101 180 mcg<br>A total of 6 subjects received single dose of 180 mcg P1101 | Drug: P1101 (180 mcg)<br>* P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 180 mcg subcutaneously.<br>|
| Experimental: P1101 225 mcg<br>A total of 6 subjects received single dose of 225 mcg P1101 | Drug: P1101 (225 mcg)<br>* P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 225 mcg subcutaneously.<br>|
| Experimental: P1101 270 mcg<br>A total of 6 subjects received single dose of 270 mcg P1101 | Drug: P1101 (270 mcg)<br>* P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 270 mcg subcutaneously.<br>|
| Active Comparator: Pegasys 180 mcg<br>A total of 12 subjects received single dose of 180 mcg Pegasys | Drug: Pegasys<br>* Pegasys for injection, 180 mcg/mL, 1.0 mL/vial, Dose/subject: 180 mcg subcutaneously.<br>* Other names: peginterferon alfa-2a;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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P1101, phase 1, healthy volunteers