Lizess PI

Question 1

indications and usage ?

Answer 1

Treatment in adults of CIC and IBS-C

Question 2

What are the dosages for linzess?

Answer 2

IBS-C 290 mcg
CIC - 145 mcg
taken once daily on an empty stomach at least 30 min prior to first meal of the day

Question 3

What are the contraindications of Linzess?

Answer 3

pediatric patients up to 6 years of age

patients with known or suspected mechanical GI obstruction

Question 4

Warnings and precautions are?

Answer 4

1. pediatric risk (avoid in patients 6-17)

2. Diarrhea

Question 5

What was most common AR?

Answer 5

Diarrhea (in pooled IBS-C and CIC doubleblind placebo controlled trials)
Severe Diarrhea reported in 2%

Question 6

What are most adverse reactions in IBS-C? (in at least 2%)

6 things
(DAFAVH)

Answer 6

Diarrhea (20% vs 3%) 
Abdominal pain (7% vs 5%) 
Flatulence (4% vs 2%) 
Abdominal distension (2% vs 1%) 
Viral gastroenteritis (3% vs 1%) 
Headache (4% vs 3%)

Question 7

What % of AR’s leading to discontinuation IBS-C?

Answer 7

IBS-C 9% vs 3%

Question 8

Most common reasons for discontinuation IBS-C?

Answer 8

DIarrhea 5% vs less than 1%

Abdominal pain 1%

Question 9

How many IBS-C patients had AE’s leading to dose reductions?

Answer 9

29% total ( diarrhea, other GI ar’s)

Question 10

What are most AR’s in CIC in at least 2% ?

6 things
DAFAUS

Answer 10

Diarrhea (16% bs 5%) 
Abdominal pain (7% vs 6%) 
Flatulence (6% vs 5%) 
Abdomin Distension (3% vs 2%) 
Upper Resp. tract infe. (5% vs 4%) 
Sinusitis (3% vs 2%)

Question 11

What % of AR’s led to discontinuation of CIC?

Answer 11

CIC - 8% vs 4%

Question 12

Most common reason for discontinuation in CIC?

Answer 12

Diarrhea 5% vs placebo 1%

Abdominal pain 1%

Question 13

What percentage of patients had adverse reactions that led to dose reduction in CIC?

Answer 13

29 % (diarrhea, other GI adverse reactions)

Question 14

What dose adjustment is needed for hepatic and renal impairment?

Answer 14

no dose adjustment needed

Question 15

What is Max recommended human dose?

Answer 15

5 mcg based on 60 kg bodyweight

Question 16

Overall mean age of IBS-C patients ?

Answer 16

44 yrs

Question 17

What % of specific patients demographics taking 290 mcg in IBS-C trials?

Answer 17

90% female
19% black
77% white
12% hispanic

Question 18

How many patients in trail 1 & 2 of IBS-C trials?

Answer 18

Trial 1 - 800

Trial 2- 804

Question 19

To be in IBS-C trials patients met Rome 2 criteria and ?

Answer 19

• mean abdominal pain score of at least 3 on 0-10 point score
• less than 3 complete spontaneous BM’s (CSBM) per week
• less than or equal to 5 SBM’s per week

Question 20

In IBS-C trials results for primary endpoints were based on what?

Answer 20

Patient diaries

Question 21

In the IBS-C 4 primary efficacy responder endpoints are based on ?

Answer 21

Patient being a weekly responder for either at least 9 out of the first 12 weeks of treatment or at least 6 out of the first 12 weeks

Question 22

In the IBS studies max efects of Linzess were seen at?

Answer 22

weeks 6-9 and were maintained until the end of the study

Question 23

What was the mean treatment difference from placebo at wk 12 in IBS-C trials?

Answer 23

Was decrease in pain score of approx. 1.0 point in both trials (using 11- point scale)

Question 24

How many patients were in trial 3 and 4 of CIC studies?

Answer 24

Trial 3 = 642

Trial 4 = 630

Question 25

What was the mean age in trial 3 and 4?

Answer 25

``` 48 years (range of 18-85) (12% at least 65) ```

Question 26

What % of specific patients demographics recieved linzess treatment 145mcg/ 290 mcg/ placebo ?

Answer 26

89% female 22% black 76% white 10% hispanic

Question 27

In CIC trials, all patients met modified Rome 2 criteria for functional constipation. This included less than 3 SBM's per week and 1 of the following symptoms for at least 12 weeks, which need not be consecuitive, in teh preceding 12 months? (3 things) (SLS)

Answer 27

1. Straining durring greater than 25% of bowel movements 2. Lumpy or hard stools durring greater than 25% of bowel movements 3. Sensation of incomplete evacuation durring greater than 25% of BM's

Question 28

What was the CSBM overall responder defined as in CIC studies?

Answer 28

patient who had at least 3 CSBM's and an increase of at least 1 CSBM from baseline in a given week for at least 9 weeks out of the 12 week treatment period

Question 29

In CIC studies Linzess _____ mcg did not consistently offer additional clinically meaningful treatment benefit over placebo than Linzess______ mcg

Answer 29

290 mcg , 145 mcg (so 145 mcg recommended in CIC)

Question 30

In CIC studies CSBM frequency reached max level durring week _____?

Answer 30

1, and was also demonstrated over remainder of 12 week treatment in trial 3 and 4

Question 31

In CIC studies, the mean change from baseline in CBSM frequency at wk 12, the difference between placebo and LInzess was aprox?

Answer 31

-1.5 CSBMs

Question 32

In both the IBS-C and CIC trails for Linzess, abdominal pain is listed as an adverse reaction that occoured at an incidence of greater than placebo. What symptoms are included under abdominal pain? (3)

Answer 32

abdominal pain upper abdominal pain lower abdominal pain

Question 33

Renee a 48 yr old woman was a participant in one of the linzess cic trials. Trial 3. After the 2 week baseline period, she started treatment and began having a CSBM every other day, compared to basline period, durring which she expirenced 1 CSBM per week. After the 12 week treatment period Renee participated in the 4 week randomized withdrawl period. Durring these 4 weeks she was dissappointed to find that her CSBM rate dropped back down to 1 per week, her baseline rate. What is the most likely explaination for what happened?

Answer 33

Renee has been given LInzess durring the 12 week treatment period and then was re-randomized to recieve placebo.

Question 34

Irwin- 45 yr old male. participant in Linzess IBS-C trials. Durring 12 week treatment period, he expirenced a 20% reduction in abdominal pain. (compared to baseline) during weeks 1-4, a 30% reduction in weeks 5-8, and 50% reduction in weeks 9-12. He also exp. 3-4 CSBM ever week, compared to baseline period, durring which he only had one CSBM over the course of two weeks. A few months prior to participating in study, Irwin was diagnosed as having IBS- C from just gastro Dr. G. Irwin asked Dr. G what prescription he could take for IBS-C, which of the follding is approved for treating his disorder? Amitiza, Miralax, Lacetlos

Answer 34

None of these are FDA approved.

Question 35

Thre first treatment often recomended by a MD for patient with constipation is?

Answer 35

changes in diet or lifestyle

Question 36

Which of the folowing is true of IBS-C or CIC diagnosis?

Answer 36

Diagnosis is based primarly of patient hist. and symptoms

Question 37

what is the MOA of mirolax?

Answer 37

Mirolax is porely absorbed by colon which causes water to diffuse in the lumen by osmosis.

Question 38

Lotronex works by effecting ____ in the digestion system?

Answer 38

serotonin receptors

Question 39

Amitiza PI warns that in patients with symptoms suggestive of _______ a through evaluation should be performed to confirm its absence prior to initiating therapy with Amitiza.

Answer 39

Mechanical gastrintestinal obstruction

Question 40

what is true of amitiza

Answer 40

amitiza is minially absorbed in the blood stream

Question 41

what is true of OTC laxatives?

Answer 41

often effective at producing bowel movements are approved for occasional constipation approved for short term treatment only

Question 42

PEG can be prescribed to patients for treatment of _______ and is FDA approved for this use ?

Answer 42

occasional constipation

Question 43

Clair is exp. constipation symptoms and heads to pharmacy to find otc agent that might help, which of the followin will she find OTC? (3)

Answer 43

metamucil mirolax correctol

Question 44

Probiotics attempt to contribute to which factor that may contribute to development of IBS-C

Answer 44

bacterial overgrowth

Question 45

What is visceral hypersensitivity?

Answer 45

Enhanced responsiveness or perception within the intestine that occurs in response to normal or abnormal events in the gut

Question 46

In the RAO study ___% of patients experienced abdominal pain every day during the 2-week pretreatment period mean baseline score was ___ for placebo and ___ for linaclotide on an 11-point scale.

Answer 46

88% 5. 6 5. 7

Question 47

In the RAO study ___% of patients had no CSBMs during 2-week pretreatment period. Mean rate was ___/week

Answer 47

76% 0.2

Question 48

Linzess caused death in ____ juvenile mice

Answer 48

Young

Question 49

___ was most common AE, experienced in ___% linzess vs. ___% placebo

Answer 49

Diarrhea 20% 3%

Question 50

___ and dehydration were reported < ___% of linzess patients

Answer 50

Fecal incontinance 1%

Question 51

In what two ways does linzess work?

Answer 51

1. Increases fluid secretion and accelerates transit | 2. Decreases pain- sensing nerve activity

Question 52

To be abdominal pain responder in IBS-C trial 1 & 2 ( 9 of 12 wks)

Answer 52

Must have 3 in abdominal pain And greater than or equal to 30% decrease in abdominal pain

Question 53

In the Chey trials ___% of patients experienced abdominal pain every day during the 2-week pre treatment period. Mean baseline was ___ on an 11 point scale.

Answer 53

87% 5.5-5.6

Question 54

In the Chey trials ___% had no CSBMs during 2-week pretreatment period. Mean rate was ___/week

Answer 54

76% .2

Question 55

In the RAO trial 1 (9 of 12 wks) for abdominal pain >/= 30% decrease was ___% vs ___% In the Chey trial 2 (9 of 12 wks) for abdominal pain >/= 30% decrease was ___% vs ___%

Answer 55

34. 3 vs. 27.1 | 38. 9 vs. 19.6

Question 56

In the RAO trial 1 (9 of 12 wks) the CSBM Resonder >/= 3 plus 1 CSBM was ___% vs ___% In the Chey trial 2 (9 of 12 wks) the CSBM Resonder >/= 3 plus 1 CSBM was ___% vs ___%

Answer 56

19.5 vs 6.3 18 vs 5

Question 57

In the RAO trial 1 (9 of 12 wks) combined responder abdominal pain & CSBM was ___% vs ___% In the Chey trial 2 (9 of 12 wks) combined responder abdominal pain & CSBM was ___% vs ___%

Answer 57

12. 1 vs 5.1 | 12. 7 vs 3

Question 58

In the RAO trial 1 (6 of 12 wks) combined Responder abdominal pain & CSBM was ___% vs ___% In the Chey trial 2 (6 of 12 wks) combined Responder abdominal pain & CSBM was ___% vs ___%

Answer 58

33. 6 vs 21 | 33. 7 vs 13.9

Question 59

In the RAO trial 1 (6 of 12 weeks) abdominal pain >/= 30% decrease was ___% vs ___% In the Chey trial 2 (6 of 12 weeks) abdominal pain >/= 30% decrease was ___% vs ___%

Answer 59

50. 1 vs 37.5 | 48. 9 vs 34.5

Question 60

In the RAO trial 1 (6 of 12 wks) CSBM responder increase >/= 1 CSBM was ___% vs ___% In the Chey trial 2 (6 of 12 wks) CSBM responder increase >/= 1 CSBM was ___% vs ___%

Answer 60

48. 6 vs 29.6 | 47. 6 vs 22.6

Question 61

In the Lembo trial 3 (9 of 12 wks) CSBM >/= 3 plus increase 1 CSBM ___% vs ___% In the Lembo trial 4 (9 of 12 wks) CSBM >/= 3 plus increase 1 CSBM ___% vs ___%

Answer 61

20. 3 vs 3.3 | 15. 5 vs 5.6

Question 62

In IBS-C trials there were ___ patients

Answer 62

1600

Question 63

In CIC trials there were ___ patients

Answer 63

1200

Question 64

What did the 2 IBS-C trials evaluate? (3 things) | ACC

Answer 64

Abdominal Pain Responders CSBM responders Combined responders

Question 65

What did CIC trials evaluate?

Answer 65

CSBM Responders based on 2 criteria 1. At least 3 CSBMs 2. An increase of at least 1 CSBM vs baseline