PK/PD and Safety Evaluation of 20kDa Peginterferon α-2a from “Unipeg®” in Healthy Human Subjects

Tasneem Ahmad. Center for Bioequivalence Studies and Bioassay Research, ICBS, University of Karchi, Appt#8, Gulshan View, Gulshan-e-Iqbal Block 13-C, Karachi, 75300, Pakistan.

Purpose: Peginterferon α-2a (20 kDa) derived from E. coli is a distinct variety of peginterferons. A pilot study of this drug (UNIPEG®) was conducted on healthy human subjects to evaluate its safety and pharmacokinetic (PK) and Pharmacodynamic (PD) behaviour in local population.

Methods: With due approval of the IEC operating under ICH-GCP guidelines ten healthy male subjects (Age: Years 25.2±5.33 (20-32); Weight: Kg 59.60±7.71(60-74) were selected randomly from the Pakistani population after thorough screening and signing of the Informed Consent Document for an Open label, Single Dose study.

Each subject received a subcutaneous injection of the drug (180 µg) in abdominal skin and blood samples were collected at 0 (pre-dose) and 1, 2, 3, 6, 12, 24, 36, 60, 84, 108, 132 and 156 hours, and analyzed by a validated ELISA for Unipeg®. The assay with a dynamic range of 900 to 7pg/mL gave an inter assay mean accuracy of 98.31% and precision of 8.59%. ( n = 18). The samples are stored at -80o C for the PD evaluation through analysis of biomarkers neopterin and β2-microglobulin. The PD work is in progress and has not concluded yet.

The safety and tolerance of the drug was evaluated by observation of Adverse Events and evaluating the change in general health parameters, haematological and biochemical test results during and after the study.

Results: Pharmacokinetics Presented as Mean±SEM (range). Cmax: 18.67±2.92 ng/ml (7.05 - 34.51); AUC0-∞: 1440±113 h.µg/l] (969 - 2101); Absorption Half-Life: 17.02±2.06 h (10.37 - 29.26); Volume of Distribution: 8.933±1.72 L (4.81 - 18.34); Clearance: 0.112±8.21ml/.h (71.96 - 155.96).

Safety: No Sever Adverse Effect was observed however the most common Adverse Event (AE) was the fever; observed in all volunteers (n = 10), headache (6), Fatigue (5), Vomiting (4) and diarrhoea, loss of appetite, body ache was observed in 3 volunteers. Three out of ten volunteers demonstrated decrease in WBC and platelets count. Insignificant changes in haematology returned to normal values within 16 days.

Conclusions: The safety profile of UNIPEG® was found very similar to those of reported in literature for unmodified IFNs and other pegylated interferons generally used in therapy. Future clinical trials are recommended to further establish the safety profile and pharmacokinetics. The work in progress for evaluating immunological and antitumor response through determination of bio-markers; neopterin and β2-microglobulin in the serum will further provide knowledge on the drug’s pharmacodynamic behaviour.