PMID- 29478239
OWN - NLM
STAT- MEDLINE
DCOM- 20180905
LR  - 20181202
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 38
IP  - 6
DP  - 2018 Jun
TI  - A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and 
      Pharmacodynamics of the Novel Dopamine D1 Receptor Partial Agonist, PF-06669571, 
      in Subjects with Idiopathic Parkinson's Disease.
PG  - 509-517
LID - 10.1007/s40261-018-0632-6 [doi]
AB  - BACKGROUND AND OBJECTIVES: There is an unmet medical need for additional 
      treatment options for Parkinson's disease. This was a Phase I, double-blind 
      clinical trial assessing safety, tolerability, pharmacokinetics, and 
      pharmacodynamics of multiple doses of the novel dopamine D1 receptor partial 
      agonist, PF-06669571, in subjects with idiopathic Parkinson's disease on a stable 
      dose of L-DOPA. METHODS: Subjects received PF-06669571 (or matching placebo) 
      titrated from 1 mg to 3 mg over 7 days. The primary pharmacodynamic endpoint was 
      the change from baseline in Movement Disorder Society-Unified Parkinson's Disease 
      Rating Scale Part III total motor score at the pharmacodynamic time of maximum 
      change from baseline on day 7. RESULTS: Twenty subjects were randomized and 19 
      completed the study. Maximum plasma concentrations (C(max)) of PF-06669571 were 
      reached 3.35 and 3.19 h post-dose on day 1 and day 7. Geometric mean C(max) and 
      area under the plasma concentration-time profile from time 0 to 24 h post-dose on 
      day 7 were 92.51 ng/mL and 1626 ng.h/mL, respectively. The primary 
      pharmacodynamic endpoint did not meet the pre-specified criteria for significant 
      improvement; however, the criteria were met in a sensitivity analysis excluding 
      data from a L-DOPA outlier (L-DOPA dose of 2550 mg/d). The most common adverse 
      events (AEs) were nausea (experienced by 2 subjects each in the PF-06669571 and 
      placebo groups). There were no permanent discontinuations or dose reductions due 
      to AEs. DISCUSSION: Multiple daily doses of PF-06669571 were safe and well 
      tolerated with no notable safety concerns. The pharmacodynamic endpoint did not 
      meet the pre-specified criteria for significant improvement. CLINICALTRIALS. GOV 
      IDENTIFIER: NCT02565628.
FAU - Gurrell, Rachel
AU  - Gurrell R
AD  - Pfizer Inc, Cambridge, MA, USA. Rachel.Gurrell@Pfizer.com.
AD  - Pfizer Inc, Granta Park, Cambridge, CB21 6GP, UK. Rachel.Gurrell@Pfizer.com.
FAU - Duvvuri, Sridhar
AU  - Duvvuri S
AD  - Pfizer Inc, Cambridge, MA, USA.
FAU - Sun, Pengling
AU  - Sun P
AD  - Pfizer Inc, Cambridge, MA, USA.
FAU - DeMartinis, Nicholas
AU  - DeMartinis N
AD  - Pfizer Inc, Cambridge, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02565628
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Dopamine Agonists)
RN  - 0 (Organic Chemicals)
RN  - 0 (PF-06669571)
RN  - 0 (Receptors, Dopamine D1)
RN  - 46627O600J (Levodopa)
SB  - IM
MH  - Aged
MH  - Dopamine Agonists/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Levodopa/administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Organic Chemicals/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Parkinson Disease/*drug therapy
MH  - Receptors, Dopamine D1/agonists
MH  - Time Factors
EDAT- 2018/02/27 06:00
MHDA- 2018/09/06 06:00
CRDT- 2018/02/26 06:00
PHST- 2018/02/27 06:00 [pubmed]
PHST- 2018/09/06 06:00 [medline]
PHST- 2018/02/26 06:00 [entrez]
AID - 10.1007/s40261-018-0632-6 [pii]
AID - 10.1007/s40261-018-0632-6 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2018 Jun;38(6):509-517. doi: 10.1007/s40261-018-0632-6.