Healthy Volunteers
Conditions
Keywords
P1101, phase 1, healthy volunteers
Brief summary
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
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.
Interventions
DRUGP1101 (24 mcg)
P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 24 mcg subcutaneously.
DRUGP1101 (48 mcg)
P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 48 mcg subcutaneously.
DRUGP1101 (90 mcg)
P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 90 mcg subcutaneously.
DRUGP1101 (180 mcg)
P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 180 mcg subcutaneously.
DRUGP1101 (225 mcg)
P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 225 mcg subcutaneously.
DRUGP1101 (270 mcg)
P1101 solution for injection, 180 mcg/mL, 1.2 mL/vial;Dose/subject: 270 mcg subcutaneously.
DRUGPegasys
Pegasys for injection, 180 mcg/mL, 1.0 mL/vial, Dose/subject: 180 mcg subcutaneously.
Sponsors
PharmaEssentia
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Intervention 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.
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| λz (Ke) of P1101 and Pegasys | 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. | The terminal elimination rate constant; calculated using linear regression on the terminal portion of the Ln-concentration versus time curve |
| Adverse Event | Through study Day 35 | Frequency and severity of all adverse events among subjects, including frequency and severity of drug-related adverse events. |
| AUC of P1101 and Pegasys | 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. | Area under the serum concentration-time curve from time 0 to infinity |
| AUC0-t of P1101 and Pegasys | 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. | Area under the serum concentration-time curve from time zero to the last measurable concentration (AUC0-t) |
| Cmax of P1101 and Pegasys | 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. | Maximum serum concentration; the highest concentration observed during a dosage interval. |
| Ct of P1101 and Pegasys | 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. | The last measured serum concentration, the last concentration above the lower limit of quantification following dose |
| Tmax of P1101 and Pegasys | 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. | The time that Cmax was observed |
| T½ of P1101 and Pegasys | 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. | Terminal elimination half-life |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2',5' oligoadenylate synthetase (OAS): Emax | Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose | Maximum serum biomarker response; the highest biomarker concentration observed during a dosage interval. |
| 2',5' oligoadenylate synthetase (OAS): Tmax | Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose | The time that Emax was observed. |
| 2',5' oligoadenylate synthetase (OAS): AUC0-t | Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose | Area under the biomarker concentration versus time curve from time 0 to the last measured concentration. |
| Neopterin: Emax | Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose | Maximum serum biomarker response; the highest biomarker concentration observed during a dosage interval. |
| Neopterin: Tmax | Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose | The time that Emax was observed. |
| Neopterin: AUC0-t | Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose | Area under the biomarker concentration versus time curve from time 0 to the last measured concentration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity | Samples were collected within 1 hour pre-dose, at 336 and 672 hours after dose administration | Analysis of the concentration of anti-P1101 antibody. |
Countries
Canada
Outcome results
None listed