Trulance™ - Plecanatide
Manufacturer: Synergy
Pharmaceuticals Inc.
FDA Approval Date: 1/19/17
Trulance™ - Plecanatide
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Trulance™ (plecanatide)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Trulance™ -
(plecanatide)
Trulance™ - Plecanatide
Clinical Application
• Indications:
• Treatment of chronic idiopathic
constipation (CIC) in adults
• Place in therapy:
• First uroguanylin analog to be approved
for the treatment of CIC, thus, provides a
differentiated therapeutic option for these
patients
Trulance [package insert].
Trulance™ - Plecanatide
Clinical Application
• Contraindications:
• Patients less than 6 years of age
• Patients with known or suspected
mechanical gastrointestinal obstruction
• Warnings and Precautions:
• Black box warning: Risk of serious
dehydration in pediatric patients
• Diarrhea: If severe diarrhea occurs,
suspend dosing and rehydrate
Trulance [package insert].
Trulance™ - Plecanatide
Clinical Application
• Pregnancy:
• Category B
• Available data on use is not sufficient to
inform any drug-associated risks for
major birth defects and miscarriage
• No evidence of harm in animal studies
• Lactation:
• No data available
Trulance [package insert].
Trulance™ - Plecanatide
Drug Facts
• Pharmacology:
• Guanylate cyclase-C (GC-C) agonist
• Structurally related to human
uroguanylin
Trulance [package insert].
Trulance™ - Plecanatide
Drug Facts
• Pharmacokinetics:
A
Minimally absorbed; AUC and Cmax
cannot be calculated
D
Minimally distributed
M
Proteolytically degraded within
intestinal lumen
E
No excretion studies conducted
Trulance [package insert].
Trulance™ - Plecanatide
Drug Interactions
• Drug Interactions – Object
Drug/Precipitant Drug:
• Neither plecanatide nor its metabolite
inhibited CYP2C9 and CYP3A4
• Does not induce CYP3A4 in vitro
• Neither substrates nor inhibitors of P-gp
or BCRP in vitro
Trulance [package insert].
Trulance™ - Plecanatide
Adverse Effects
• Common Adverse Effects:
(Plecanatide%)[placebo%]
• Diarrhea (5%)[1%]
• Serious Adverse Effects:
(Plecanatide%)[placebo%]
• Severe diarrhea (0.6%)[0.3%]
Trulance [package insert].
Trulance™ - Plecanatide
Monitoring Parameters
• Efficacy Monitoring:
• Frequency of bowel movements
• Toxicity Monitoring:
• No findings of toxicity observed in
studies
Trulance [package insert].
Trulance™ - Plecanatide
Prescription Information
• Dosing: 3 mg by mouth once daily
• Cost: Not yet available
Trulance [package insert].
Trulance™ - Plecanatide
Literature Review
• Purpose:
• To assess the efficacy and safety of two
plecanatide doses when administered to
patients with CIC for 12 weeks
• Design:
• Phase III, multi-center, double-blind,
placebo-controlled study
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Literature Review
• Treatment Arms:
• 1:1:1 ratio
• Plecanatide 3 mg
• Plecanatide 6 mg
• Placebo
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Literature Review
• Inclusion Criteria:
• Patients with CIC aged 18-80 years old
• Body mass index of 18-40 kg/m2
• Rome III functional constipation criteria
• History of < 3 bowel movements per week
• No use of manual maneuvers to facilitate defecations
• At least two of the following for ≥25% of defecations:
• Straining
• Lumpy or hard stool
• Sensation of incomplete evacuation
• Sensation of anorectal blockage/obstruction
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Literature Review
• Exclusion Criteria:
• Met Rome III criteria for irritable bowel
syndrome
• Diseases or conditions associated with
constipation
• Diseases of conditions that affect GI
motility or defecation
• Medical history of cancer
• Other uncontrolled medical conditions
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Literature Review
• Patient Characteristics:
• Female (80.8%)
Plecanatide Plecanatide
3 mg
6 mg
• Black/African American
(25.6%)
Placebo
(n=452)
(n=453)
(n=441)
Age
45.1
46.4
45.0
Gender (% female)
81.2
82.1
79.0
Race (% black)
24.5
23.9
28.5
0.3
0.4
0.3
CSBMs/week
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Literature Review
• Efficacy Results:
Endpoint
Plecanatide
3 mg
(n=453)
Plecanatide
6 mg
(n=441)
Placebo
(n=452)
Durable
overall
CSBM
responders
21.0%
p<0.001
19.5%
p<0.001
10.2%
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Literature Review
• Treatment-Emergent Adverse Events:
Plecanatide Plecanatide
Placebo
3 mg
6 mg
(n=458)
(n=474)
(n=457)
Diarrhea
5.9%
5.7%
1.3%
Nasopharyngitis
0.8%
2.4%
1.7%
Sinusitis
2.1%
0.7%
0.7%
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Literature Review
• Conclusions:
• Plecanatide, orally administered once
daily for 12 weeks, significantly improved
constipation and its related symptoms
• Plecanatide was well-tolerated, exhibiting
a limited adverse effect profile
Miner PB Jr, et al. Am J Gastroenterol. 2017.
Trulance™ - Plecanatide
Summary
• TrulanceTM, plecanatide, is a guanylate cyclase-C
agonist indicated in adults for treatment of CIC
• Plecanatide is dosed 3mg once daily
• The most common adverse effect is diarrhea. If
severe diarrhea occurs, suspend dosing and
rehydrate.
• Plecanatide is contraindicated in patients less than
6 years old due to the risk of serious dehydration
• Plecanatide provides a new option for patients with
CIC who have not found relief in other medications
Trulance™ - Plecanatide
References
1.
www.trulancehcp.com
2.
Trulance [package insert]. New York, NY:
Synergy Pharmaceuticals Inc.; January 2017.
3.
Miner PB Jr, Koltun WD, Wiener GJ, De La
Portilla M, Prieto B, Shailubhai K, Layton MB,
Barrow L, Magnus L, Griffin PH. A randomized
phase III clinical trial of plecanatide, a
uroguanylin analog, in patients with chronic
idiopathic constipation. Am J Gastroenterol 2017.
doi: 10.1038/ajg.2015.611. [Epub ahead of print]