PMID- 26152132
OWN - NLM
STAT- MEDLINE
DCOM- 20151109
LR  - 20150822
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 53
IP  - 9
DP  - 2015 Sep
TI  - Bioequivalence of different dose-strength tablets of selexipag, a selective 
      prostacyclin receptor agonist, in a multiple-dose up-titration study.
PG  - 788-98
LID - 10.5414/CP202318 [doi]
AB  - OBJECTIVE: Selexipag is a novel, oral, selective prostacyclin (PGI2) receptor 
      agonist in clinical development for the treatment of pulmonary arterial 
      hypertension. Film-coated tablets with strength between 200 and 1,600 mug were 
      used. Bioequivalence between 8 x 200 mug and a new 1,600 mug tablet was evaluated 
      at steady state in healthy male subjects. MATERIALS AND METHODS: This was an 
      open-label, 2-treatment, 2-period, crossover, up-titration, phase 1 study. The 
      treatments were selexipag at 1,600 mug b.i.d. for 4.5 days either as 8 x 200 mug 
      tablets (reference: A) or 1 x 1,600 mug tablet (test: B), both preceded by an 
      up-titration phase starting from 400 mug b.i.d. doses, in 200-mug steps every 4th 
      day. Subjects were randomized 1 : 1 to the A-B or B-A sequence. The 
      pharmacokinetics and tolerability of selexipag and its active metabolite, 
      ACT-333679, were investigated. RESULTS: 80 subjects were enrolled in the study: 
      65 subjects completed the study according to protocol, and 15 subjects withdrew 
      from the study. The most frequent adverse events (AEs) were headache (86%), 
      myalgia (73%), and jaw pain (73%). There was no difference in nature and overall 
      frequency of AEs between the two treatments. Steady state was attained within 3 
      days of the selexipag 1,600 I(1/4)g b.i.d. TREATMENTS: The 90% confidence intervals 
      (CIs) of the geometric mean ratio (B/A) at steady state for AUCI„ and Cmax,ss 
      were within (0.80, 1.25) bioequivalence interval: (0.92, 1.06) and (0.95, 1.14), 
      respectively, for selexipag and (0.95, 1.06) and (0.94, 1.07), respectively, for 
      the active metabolite, ACT-333679. CONCLUSIONS: Bioequivalence was demonstrated 
      between 8 x 200 mug and 1 x 1,600 mug selexipag at steady state.
FAU - Baldoni, Daniela
AU  - Baldoni D
FAU - Bruderer, Shirin
AU  - Bruderer S
FAU - Muhsen, Naguib
AU  - Muhsen N
FAU - Dingemanse, Jasper
AU  - Dingemanse J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Acetamides)
RN  - 0 (Pyrazines)
RN  - 0 (Receptors, Epoprostenol)
RN  - 0 (Tablets)
RN  - 5EXC0E384L (selexipag)
SB  - IM
MH  - Acetamides/administration & dosage/adverse effects/*pharmacokinetics
MH  - Adult
MH  - Cross-Over Studies
MH  - Humans
MH  - Male
MH  - Prospective Studies
MH  - Pyrazines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Receptors, Epoprostenol/*agonists
MH  - Tablets
MH  - Therapeutic Equivalency
EDAT- 2015/07/15 06:00
MHDA- 2015/11/10 06:00
CRDT- 2015/07/09 06:00
PHST- 2015/08/21 00:00 [accepted]
PHST- 2015/07/09 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/11/10 06:00 [medline]
AID - 13556 [pii]
AID - 10.5414/CP202318 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2015 Sep;53(9):788-98. doi: 10.5414/CP202318.