PMID- 33236287
OWN - NLM
STAT- MEDLINE
DCOM- 20210202
LR  - 20210202
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 41
IP  - 1
DP  - 2021 Jan
TI  - Single-Dose Pharmacokinetics, Pharmacodynamics and Immunogenicity, and 
      Multiple-Dose Immunogenicity of INTP5 (Pegfilgrastim Biosimilar) Versus Reference 
      Pegfilgrastim in Healthy Subjects.
PG  - 29-42
LID - 10.1007/s40261-020-00987-3 [doi]
AB  - BACKGROUND AND OBJECTIVE: INTP5 has been developed as a pegfilgrastim 
      biosimilar. Single-dose, crossover study compared the pharmacokinetics and 
      pharmacodynamics (PK/PD) of INTP5 (pegfilgrastim biosimilar) with reference 
      pegfilgrastim (Neulasta((R)), pegfilgrastim-ref) and a multiple-dose, 
      parallel-group study compared the immunogenicity of INTP5 with pegfilgrastim-ref 
      in healthy subjects as part of a complete clinical development plan. METHODS: In 
      the PK/PD study, subjects received a single subcutaneous 6 mg dose of INTP5 and 
      pegfilgrastim-ref (N = 142) separated by a 6-week washout period. The primary 
      endpoints were area under the serum concentration-time curve measured from time 
      zero to infinity (AUC(0-infinity)) and maximum measured serum concentration (C(max)) of 
      pegfilgrastim and area under the absolute neutrophil count (ANC) versus time 
      curve from time zero to t (AUEC(0-t)) and maximum measured ANC (E(max)) of 
      baseline non-adjusted ANCs. In the immunogenicity study, subjects received two 
      6 mg doses of INTP5 (N = 100) or pegfilgrastim-ref (N = 100) separated by 
      21 days. The primary endpoints were incidence of anti-drug antibodies (ADAs) in 
      the two treatment groups. RESULTS: The primary PK endpoints [AUC(0-infinity) (90% CI 
      108.59-123.11) and C(max) (106.24-118.99)] and the primary PD endpoints 
      [AUEC(0-t) (99.07-102.32) and E(max) (100.24-104.25)] met the acceptance criteria 
      of 80-125%. The incidence of ADAs was 10.6% in the INTP5 arm and 9.0% in the 
      pegfilgrastim-ref arm. The 90% CI for risk difference of the ADA incidence 
      between INTP5 and pegfilgrastim-ref was 1.64% (- 5.40 to 8.68) and was within the 
      10% margin. No neutralizing antibodies were reported. Immunogenicity did not 
      impact PK/PD parameters and subjects with aberrant PK/PD/safety did not show 
      immunogenicity concerns. Incidence of adverse events (AEs) was similar with INTP5 
      and pegfilgrastim-ref in both studies. The most common AEs were musculoskeletal 
      pain and headache. CONCLUSION: INTP5 showed PK/PD equivalence with 
      pegfilgrastim-ref following a single dose, no clinically meaningful difference in 
      the immune response following multiple doses, and a comparable safety profile.
FAU - Singh, Inderjeet
AU  - Singh I
AD  - Intas Pharmaceuticals Ltd. (Biopharma), Plot No: 423/P/A, Sarkhej-Bavla Highway, 
      Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India.
FAU - Attrey, Anshul
AU  - Attrey A
AD  - Lambda Therapeutic Research Ltd., Lambda House, Plot No. 38, Survey No. 388, Near 
      Silver Oak Club, S. G. Highway, Gota, Ahmedabad, Gujarat, 382481, India.
FAU - Garg, Adarsh
AU  - Garg A
AD  - Lambda Therapeutic Research Ltd., Lambda House, Plot No. 38, Survey No. 388, Near 
      Silver Oak Club, S. G. Highway, Gota, Ahmedabad, Gujarat, 382481, India.
FAU - Patel, Ronak
AU  - Patel R
AD  - Lambda Therapeutic Research Ltd., Lambda House, Plot No. 38, Survey No. 388, Near 
      Silver Oak Club, S. G. Highway, Gota, Ahmedabad, Gujarat, 382481, India.
FAU - Jose, Vinu
AU  - Jose V
AUID- ORCID: 0000-0001-6164-0632
AD  - Intas Pharmaceuticals Ltd. (Biopharma), Plot No: 423/P/A, Sarkhej-Bavla Highway, 
      Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India. vinu_jose@intaspharma.com.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20201124
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Biosimilar Pharmaceuticals)
RN  - 3A58010674 (pegfilgrastim)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - PVI5M0M1GW (Filgrastim)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Biosimilar Pharmaceuticals/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Cross-Over Studies
MH  - Female
MH  - Filgrastim/*administration & dosage/adverse effects/pharmacokinetics
MH  - Headache/chemically induced
MH  - Humans
MH  - Leukocyte Count
MH  - Male
MH  - Musculoskeletal Pain/chemically induced
MH  - Neutrophils/drug effects
MH  - Polyethylene Glycols/*administration & dosage/adverse effects/pharmacokinetics
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2020/11/26 06:00
MHDA- 2021/02/03 06:00
CRDT- 2020/11/25 05:49
PHST- 2020/11/05 00:00 [accepted]
PHST- 2020/11/26 06:00 [pubmed]
PHST- 2021/02/03 06:00 [medline]
PHST- 2020/11/25 05:49 [entrez]
AID - 10.1007/s40261-020-00987-3 [pii]
AID - 10.1007/s40261-020-00987-3 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2021 Jan;41(1):29-42. doi: 10.1007/s40261-020-00987-3. Epub 
      2020 Nov 24.