Drug Trial Snapshot: PIZENSY
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the PIZENSY Prescribing Information for complete information.
PIZENSY (lactitol)
Pi zen’ zee
Braintree Laboratories, Inc.
Approval date: February 12, 2020
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
PIZENSY is used to treat a type of constipation called chronic idiopathic constipation (CIC) in adults.
Idiopathic means that the cause of the constipation is unknown.
How is this drug used?
PIZENSY is a powder. The content of two packets or bottle caps should be mixed with a common beverage and taken once a day. The content of one packet or bottle cap can be taken once a day if the patient develops persistent loose stools with intake of two packets or bottle caps.
What are the benefits of this drug?
More patients who received PIZENSY experienced an increase in the number of complete spontaneous bowel movements (CSBMs) to at least 3 bowel movements per week than those who received placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Patients who entered the trial had a history of chronic constipation which included having less than 3 bowel movements per week over the 2-week screening period. Efficacy was assessed using information provided by patients daily in an electronic diary. A responder was defined as a patient who had at least 3 CSBMs in a given week and an increase of at least 1 CSBM from baseline in the same week for at least 9 weeks out of the 12-week treatment period and at least 3 of the last 4 weeks (Weeks 9-12).
The table below summarizes efficacy results for the clinical trial based on the primary efficacy endpoint.
Table 1. Efficacy Responder Rates in Placebo-Controlled Trial (Trial 1) in Adults with CIC
|
|
PIZENSY N=291a |
Placebo N=303 |
Treatment Difference (95% CI) |
|---|---|---|---|
|
Responderb |
25% |
13% |
12%c (6.0, 18.5) |
CI = confidence interval.
a 74 of 291 patients in the PIZENSY group at least temporarily reduced their dose.
b primary endpoint defined as a patient who had at least 3 CSBMs in a given week and an increase of at least 1 CSBM from baseline the same week for at least 9 weeks out of the 12-week treatment period and at least 3 of the last 4 weeks of the study.
c p-value <0.05 for difference from control.
PIZENSY Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: PIZENSY worked similarly in men and women.
- Race: PIZENSY worked similarly in White and Black or African American patients. The number of patients in other races was limited; therefore, differences in response among all races could not be determined.
- Age: PIZENSY worked similarly in patients younger than 65 years and 65 years or older.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The figure below summarizes efficacy results by subgroup for Trial 1.
Figure 5. Subgroup Analyses for CSBM Responders (Trial 1)
BLI400=PIZENSY
FDA Review
What are the possible side effects?
The most common side effects of PIZENSY are upper respiratory infections, gassiness, diarrhea, increased blood creatinine phosphokinase (a type of enzyme), belly distention and increased blood pressure.
What are the possible side effects?
The table below summarizes adverse reactions that were reported in at least 3% of patients in the PIZENSY treatment group with higher incidence than placebo.
Table 2. Common Adverse Reactions1 Reported in Adult Patients with CIC in Trial 1
|
|
PIZENSY2 (N=291) |
Placebo (N=302) |
|---|---|---|
|
Upper Respiratory Tract Infection3 |
25 (9) |
19 (6) |
|
Flatulence |
23 (8) |
8 (3) |
|
Diarrhea |
13 (4) |
9 (3) |
|
Increased Blood Creatinine Phosphokinase4 |
12 (4) |
9 (3) |
|
Abdominal Distension |
10 (3) |
2 (1) |
|
Increased blood pressure5 |
9 (3) |
2 (1) |
1 Reported in at least 3% of patients and greater than placebo.
2 74 of 291 patients in the PIZENSY group at least temporarily reduced their dose.
3 Upper respiratory tract infection includes terms viral upper respiratory tract infection and nasopharyngitis.
4 Increased blood creatinine phosphokinase includes the term blood creatinine phosphokinase MB increased.
5 Increased blood pressure includes term Hypertension
PIZENSY Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in men and women.
- Race: The occurrence of side effects was similar in White and Black or African American patients. The number of patients in other races was limited; therefore, differences in side effects among all races could not be determined.
- Age: The occurrence of side effects was similar in patients younger than 65 years and 65 years or older.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes subgroups of patients who reported any treatment emergent adverse event (TEAE) during clinical trial.
Table 3. Subgroup Analysis of TEAEs in Trial 1
|
Subgroup |
PIZENSY |
Placebo |
||
|---|---|---|---|---|
|
|
x (%) |
Total, n |
x (%) |
Total, n |
|
Any TEAEs |
143 (49%) |
291 |
136 (45%) |
302 |
|
Sex |
||||
|
Male |
29 (38%) |
76 |
25 (38%) |
65 |
|
Female |
114 (53%) |
215 |
111 (47%) |
237 |
|
Race |
||||
|
White |
85 (46%) |
184 |
80 (45%) |
177 |
|
Black or African American |
42 (51%) |
83 |
40 (40%) |
100 |
|
Asian |
12 (63%) |
19 |
12 (57%) |
21 |
|
Other |
4 (80%) |
5 |
4 (100%) |
4 |
|
Age Group |
||||
|
< 65 years |
107 (50%) |
212 |
101 (46%) |
220 |
|
≥ 65 years |
36 (46%) |
79 |
35 (43%) |
82 |
|
Ethnicity |
||||
|
Hispanic or Latino |
36 (31%) |
115 |
43 (38%) |
113 |
|
Not Hispanic or Latino |
107 (61%) |
176 |
93 (49%) |
189 |
Clinical Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved PIZENSY based on evidence from a clinical trial (Trial 1/ NCT02819297) of 594 patients with CIC. This trial was conducted in the USA.
The FDA also considered other supportive evidence including data from Trial 2 (NCT02481947) which compared PIZENSY to previously approved drug (lubiprostone) for CIC, and Trial 3 (NCT02819310) in which patients used PIZENSY for one year as well as data from published literature.
The figure below summarizes how many men and women were in the clinical trial 1.
Figure 1. Demographics by Sex
FDA Review
Figure 2 below summarizes the percentage of patients by race in the clinical trial 1.
Figure 2. Demographics by Race
*Includes American Indian or Alaska Native and Other
FDA Review
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial 1.
Figure 3. Demographics by Age
FDA Review
Figure 4. Demographics by Ethnicity
FDA Review
Who participated in the trials?
The table below summarizes demographics of patients in the clinical trials.
Table 4. Demographics for Trial 1 Population
|
Demographic Parameters |
Treatment Group(s) |
Total |
|
|---|---|---|---|
|
PIZENSY |
Placebo |
||
|
Sex |
|||
|
Men |
75 (26%) |
65 (22%) |
140 (24%) |
|
Women |
216 (74%) |
238 (78%) |
454 (76%) |
|
Race |
|||
|
White |
182 (62%) |
177 (58%) |
359 (60%) |
|
Black or African American |
85 (29%) |
101 (33%) |
186 (31%) |
|
Asian |
19 (7%) |
21 (7%) |
40 (7%) |
|
American Indian or Alaska Native |
0 |
1 (<1%) |
1 (<1%) |
|
Other |
5 (2%) |
3 (1%) |
8 (1%) |
|
Age |
|||
|
Mean years (SD) |
52.5 (15.3) |
51.0 (15.9) |
51.7 (15.6) |
|
Median (years) |
53 |
51 |
52 |
|
Min, Max (years) |
18, 88 |
19, 85 |
18, 88 |
|
Age Group |
|||
|
< 65 years |
214 (73%) |
221 (73%) |
435 (73%) |
|
≥ 65 years |
77 (27%) |
82 (27%) |
159 (27%) |
|
Ethnicity |
|||
|
Hispanic or Latino |
113 (39%) |
113 (37%) |
226 (38%) |
|
Not Hispanic or Latino |
178 (61%) |
190 (63%) |
368 (62%) |
|
Region |
|||
|
United States |
291 (100%) |
303 (100%) |
594 (100%) |
FDA Review
How were the trials designed?
The benefit and side effects of PIZENSY were evaluated in a clinical trial (Trial 1) of 594 patients with CIC. In this trial, patients received treatment with either PIZENSY or placebo once daily for 6 months. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.
Based on the information from their electronic diaries, patients were evaluated for improvement in CSBMs during the first 12 weeks of the treatment.
The FDA considered additional data from 2 more trials for supportive evidence.
In the second trial (Trial 2) of three months duration, improvement in CSBMs was used to compare PIZENSY to the drug lubiprostone which was previously approved for CIC. The third trial (Trial 3) was used to collect the side effects in patients treated with PIZENSY for one year.
How were the trials designed?
The safety and efficacy of PIZENSY were established in a randomized, double-blind, placebo-controlled trial of 6 months duration. All patients had less than 3 bowel movements per week and at least one additional constipation-related symptom for at least 12 weeks (which need not be consecutive) in the preceding 12 months.
Patients received either 20 g of PIZENSY or placebo daily. Patients who develop persistent diarrhea or loose stools could reduce their dose to 10 g of PIZENSY daily. The primary efficacy outcome measure was the proportion of patients who achieved at least 3 complete spontaneous bowel movements (CSBMs) in a given week and an increase of at least 1 CSBM from baseline in the same week for at least 9 weeks out of the 12-week treatment period.
Additionally, two trials provided supportive evidence:
- an active control, double-blind, double-dummy trial of three months duration utilizing the same endpoint
- an uncontrolled safety trial of one-year duration.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.