Clinical data for CIC

Indication

AMITIZA (lubiprostone) capsules are indicated for the treatment of Chronic Idiopathic Constipation (CIC) in adults (24 mcg twice daily).

AMITIZA clinical data for CIC

Clinical studies demonstrated an improvement in spontaneous bowel movement (SBM) frequency in adult patients with Chronic Idiopathic Constipation (CIC).1 AMITIZA also provides rapid relief—defined as onset within 24 hours after administration—for patients with CIC.

STUDY DESIGN

Two multicenter, double-blind, randomized, placebo-controlled, 4-week studies were conducted in patients with chronic idiopathic constipation.1,5,6

CIC was defined as1

Average of < 3 spontaneous bowel movements (SBMs) per week with 1 or more of the following symptoms for at least 6 months:

  • Very hard stools for at least a quarter of all bowel movements
  • Sensation of incomplete evacuation following at least a quarter of all bowel movements
  • Straining with defecation at least a quarter of the time

SBMs were defined as any bowel movements occurring in the absence of laxative use.1

SBM frequency and CIC symptoms

Spontaneous bowel movement (SBM) weekly frequency: Pivotal study results1,5,6

SBM frequency and CIC symptoms
Patient population: intent-to-treat, last observation carried forward

AMITIZA significantly increased SBMs compared to placebo during Week 1.1,5,6

AMITIZA provides improvement of CIC symptoms with consistent results1

  • In two 4-week clinical studies, symptoms evaluated were abdominal bloating, abdominal discomfort, stool consistency, straining, and constipation severity
    • Results were consistent in subpopulation analyses for gender, race, and patients ≥ 65 years of age

Rapid relief (rapid relief is defined as SBMs within the first 24 hours)

AMITIZA provides rapid relief for appropriate adult patients with CIC. Rapid relief is defined as SBMs within the first 24 hours.1

Patients with SBMs in First 24 hours: Pivotal study results1,5,7

Rapid relief (Rapid relief is defined as spontaneous bowel movements within the first 24 hours)
Patient population: intent-to-treat, last observation carried forward
Data shown are secondary endpoints

Up to 63% of patients had an SBM within 24 hours.1

Efficacy profile in adults 65 years and older

These results are from a pooled secondary subpopulation analysis based on data combined from 4-week pivotal studies 1 and 2, and one 3-week study, all multicenter, double-blind, randomized, placebo-controlled studies of patients with chronic idiopathic constipation.7

SBM Weekly frequency: Patients 65 years and older vs those under 65 years7

SBM frequency
Patient population: intent-to-treat, last observation carried forward

Improvement in constipation-related symptoms was comparable in patients 65 years and older

  • Average number of weekly SBMs in patients ≥ 65 was 6.1 at Week 4 (n=23)7
  • Average number of SBMs at Week 4: patients ≥ 65 on placebo, 3.2 (n=29); patients < 65 on AMITIZA, 5.2 (n=204); patients < 65 on placebo, 3.2 (n=209)7
  • The efficacy of AMITIZA in the elderly (≥ 65 years of age) subpopulation was consistent with the efficacy in the overall study population.1 Of the total number of constipated patients treated in the dose-finding, efficacy, and long-term studies of AMITIZA, 15.5% were ≥ 65 years of age, and 4.2% were ≥ 75 years of age

The average number of weekly SBMs increased up to 6.1 in patients ≥ 65 years at Week 4.7

SBM frequency by gender

These results are from a pooled secondary subpopulation analysis based on data combined from 4-week pivotal studies 1 and 2, both multicenter, double-blind, randomized, placebo-controlled studies of patients with chronic idiopathic constipation.7

SBM weekly frequency in men with CIC7

SBM frequency in men with CIC
Patient population: intent-to-treat, last observation carried forward

SBM weekly frequency in women with CIC7

SBM frequency in women with CIC
Patient population: intent-to-treat, last observation carried forward

The average number of weekly SBMs increased in both genders with CIC7

The mean weekly SBM rate was higher in the AMITIZA-treated group for both genders when these groups were analyzed separately.7 Statistical significance at Weeks 1, 2, and 3 was achieved in men and at Weeks 1, 2, 3, and 4 in women.

AMITIZA withdrawal study in CIC

During a 7-week randomized withdrawal study, patients with CIC who received AMITIZA during a 4-week treatment period were then randomized to receive either placebo or to continue treatment with AMITIZA.1

  • Spontaneous bowel movement (SBM) frequency rates returned toward baseline within 1 week and did not result in worsening compared to baseline for AMITIZA-treated patients randomized to placebo
  • Patients who continued on AMITIZA maintained their response to therapy over the additional 3 weeks of treatment

Important Safety Information

AMITIZA (lubiprostone) is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider (HCP) to confirm the absence of such an obstruction prior to initiating AMITIZA treatment.

AMITIZA (lubiprostone) is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider (HCP) to confirm the absence of such an obstruction prior to initiating AMITIZA treatment.

Patients taking AMITIZA may experience nausea. Concomitant administration of food with AMITIZA may reduce symptoms of nausea.

Avoid use of AMITIZA in patients with severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Instruct patients to discontinue AMITIZA and contact their HCP if severe diarrhea occurs.

Syncope and hypotension have been reported with AMITIZA in the postmarketing setting and a few of these adverse reactions resulted in hospitalization. Most reports occurred in patients taking 24 mcg twice daily. Patients should be aware that the risk of syncope and hypotension may be increased with concomitant diarrhea, vomiting, or use of medications known to lower blood pressure. Inform patients that syncope and hypotension may occur within an hour of the first dose or subsequent doses of AMITIZA and generally resolve prior to the next dose, but may recur with repeat dosing. Instruct patients to discontinue AMITIZA and contact their HCP if these reactions occur.

Dyspnea may occur within an hour of first dose. This symptom generally resolves within three hours, but may recur with repeat dosing. Instruct patients to contact their HCP if dyspnea occurs. Some patients have discontinued therapy because of dyspnea.

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=1113 vs N=316, respectively) in patients with CIC, the most common adverse reactions (incidence > 4%) were nausea (29% vs 3%), diarrhea (12% vs 1%), headache (11% vs 5%), abdominal pain (8% vs 3%), abdominal distension (6% vs 2%), and flatulence (6% vs 2%).

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=860 vs N=632, respectively) in patients with OIC, the most common adverse reactions (incidence > 4%) were nausea (11% vs 5%) and diarrhea (8% vs 2%).

In clinical trials of AMITIZA (8 mcg twice daily vs placebo; N=1011 vs N=435, respectively) in patients with IBS-C, the most common adverse reactions (incidence > 4%) were nausea (8% vs 4%), diarrhea (7% vs 4%), and abdominal pain (5% vs 5%).

Concomitant use of diphenylheptane opioids (e.g., methadone) may interfere with the efficacy of AMITIZA.

The safety of AMITIZA in pregnancy has not been evaluated in humans. Based on animal data, AMITIZA may cause fetal harm. AMITIZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when AMITIZA is administered to a nursing woman. Advise nursing women to monitor infants for diarrhea.

Reduce the dosage in CIC and OIC patients with moderate and severe hepatic impairment. Reduce the dosage in IBS-C patients with severe hepatic impairment.

Indications

AMITIZA (lubiprostone) capsules are indicated for the treatment of Chronic Idiopathic Constipation (CIC) in adults and Opioid-Induced Constipation (OIC) in adults with chronic, non-cancer pain (24 mcg twice daily). The effectiveness in patients with OIC taking diphenylheptane opioids (e.g., methadone) has not been established. AMITIZA is also indicated for Irritable Bowel Syndrome with Constipation (IBS-C) in women ≥ 18 years old (8 mcg twice daily).

Please click here for complete Prescribing Information.
  1. AMITIZA (lubiprostone) Prescribing Information. Sucampo Pharma Americas, LLC.
  2. Hall JE. Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier; 2011:773-788.
  3. Keely SJ, Montrose MH, Barrett KE. In: Yamada T, Alpers DH, Kalloo AN, Kaplowitz N, Owyang C, Powell DW, eds. Textbook of Gastroenterology. 5th ed. West Sussex, England: John Wiley & Sons Ltd; 2009:330-367.
  4. Data on file. Takeda Pharmaceuticals.
  5. Johanson JF, Morton D, Geenen J, Ueno R. Am J Gastroenterol. 2008;103:170-177.
  6. Barish CF, Drossman D, Johanson JF, Ueno R. Dig Dis Sci. 2010;55:1090-1097.
  7. Data on file. Sucampo Pharma Americas, LLC.

Important Safety Information

AMITIZA (lubiprostone) is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider (HCP) to confirm the absence of such an obstruction prior to initiating AMITIZA treatment.

AMITIZA (lubiprostone) is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider (HCP) to confirm the absence of such an obstruction prior to initiating AMITIZA treatment.

Patients taking AMITIZA may experience nausea. Concomitant administration of food with AMITIZA may reduce symptoms of nausea.

Avoid use of AMITIZA in patients with severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Instruct patients to discontinue AMITIZA and contact their HCP if severe diarrhea occurs.

Syncope and hypotension have been reported with AMITIZA in the postmarketing setting and a few of these adverse reactions resulted in hospitalization. Most reports occurred in patients taking 24 mcg twice daily. Patients should be aware that the risk of syncope and hypotension may be increased with concomitant diarrhea, vomiting, or use of medications known to lower blood pressure. Inform patients that syncope and hypotension may occur within an hour of the first dose or subsequent doses of AMITIZA and generally resolve prior to the next dose, but may recur with repeat dosing. Instruct patients to discontinue AMITIZA and contact their HCP if these reactions occur.

Dyspnea may occur within an hour of first dose. This symptom generally resolves within three hours, but may recur with repeat dosing. Instruct patients to contact their HCP if dyspnea occurs. Some patients have discontinued therapy because of dyspnea.

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=1113 vs N=316, respectively) in patients with CIC, the most common adverse reactions (incidence > 4%) were nausea (29% vs 3%), diarrhea (12% vs 1%), headache (11% vs 5%), abdominal pain (8% vs 3%), abdominal distension (6% vs 2%), and flatulence (6% vs 2%).

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=860 vs N=632, respectively) in patients with OIC, the most common adverse reactions (incidence > 4%) were nausea (11% vs 5%) and diarrhea (8% vs 2%).

In clinical trials of AMITIZA (8 mcg twice daily vs placebo; N=1011 vs N=435, respectively) in patients with IBS-C, the most common adverse reactions (incidence > 4%) were nausea (8% vs 4%), diarrhea (7% vs 4%), and abdominal pain (5% vs 5%).

Concomitant use of diphenylheptane opioids (e.g., methadone) may interfere with the efficacy of AMITIZA.

The safety of AMITIZA in pregnancy has not been evaluated in humans. Based on animal data, AMITIZA may cause fetal harm. AMITIZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when AMITIZA is administered to a nursing woman. Advise nursing women to monitor infants for diarrhea.

Reduce the dosage in CIC and OIC patients with moderate and severe hepatic impairment. Reduce the dosage in IBS-C patients with severe hepatic impairment.

Indications

AMITIZA (lubiprostone) capsules are indicated for the treatment of Chronic Idiopathic Constipation (CIC) in adults and Opioid-Induced Constipation (OIC) in adults with chronic, non-cancer pain (24 mcg twice daily). The effectiveness in patients with OIC taking diphenylheptane opioids (e.g., methadone) has not been established. AMITIZA is also indicated for Irritable Bowel Syndrome with Constipation (IBS-C) in women ≥ 18 years old (8 mcg twice daily).

Please click here for complete Prescribing Information.
  1. AMITIZA (lubiprostone) Prescribing Information. Sucampo Pharma Americas, LLC.
  2. Hall JE. Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier; 2011:773-788.
  3. Keely SJ, Montrose MH, Barrett KE. In: Yamada T, Alpers DH, Kalloo AN, Kaplowitz N, Owyang C, Powell DW, eds. Textbook of Gastroenterology. 5th ed. West Sussex, England: John Wiley & Sons Ltd; 2009:330-367.
  4. Data on file. Takeda Pharmaceuticals.
  5. Johanson JF, Morton D, Geenen J, Ueno R. Am J Gastroenterol. 2008;103:170-177.
  6. Barish CF, Drossman D, Johanson JF, Ueno R. Dig Dis Sci. 2010;55:1090-1097.
  7. Data on file. Sucampo Pharma Americas, LLC.