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Drug Trials Snapshots: IBSRELA

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 IBSRELA Prescribing Information for complete information.

IBSRELA (tenapanor)
(ibs rel`a)
Ardelyx
Approval date: September 12, 2019


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

IBSRELA is a treatment for adults with a disease of the gut called irritable bowel syndrome with constipation commonly referred to as IBS-C.

How is this drug used?

IBSRELA is a tablet taken by mouth two times each day.

What are the benefits of this drug?

Higher proportion of patients who received IBSRELA experienced a decrease in abdominal pain and more frequent bowel movements in comparison to patients who received placebo.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes the efficacy results for each trial based on daily diary entries. In both trials, the primary endpoint was the proportion of responders. A responder was defined as a patient achieving both the abdominal pain intensity and stool frequency criteria in the same week for at least 6 of the first 12 weeks of treatment.

Table 2. Efficacy Responder Rates in Placebo-Controlled Trials (Trial 1 and Trial 2) in Adults with IBS-C: Responder for at least 6 of the First 12 Weeks of Treatment

Trial 1
  IBSRELA
N=293
Placebo
N=300
Treatment Difference
[95% CIa]
Responderb

Components of Responder Endpoint:
CSBM Responderc
Abdominal Pain Responderd
37%


47%
50%
24%


33%
38%
13%
[6%, 20%]
Trial 2
Responder Rates IBSRELA
N=307
Placebo
N=299
Treatment Difference
[95% CIa]
Responderb

Components of Responder Endpoint:
CSBM Responderc
Abdominal Pain Responderd
27%


34%
44%
19%


29%
33%
8%
[2%, 15%]

a CI: Confidence Interval
bA responder for these trials was defined as a patient who met both the abdominal pain and CSBM weekly responder criteria for at least 6 of the first 12 weeks.
cA CSBM responder was defined as a patient who achieved an increase in at least 1 CSBM per week, from baseline, for a least 6 of at least 12 weeks.
dAn abdominal pain responder was defined as a patient who met the criteria of at least 30% reduction from baseline in weekly average of the worst daily abdominal pain, for at least 6 of the first 12 weeks.

Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: The majority of patients in the trials were women. IBSRELA was similarly effective in men and women.
  • Race: IBSRELA was similarly effective in different races.
  • Age: IBSRELA was similarly effective in patients younger and older than 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The tables below summarize the results for the primary endpoint in the trial by subgroup.

Table 3. Subgroup Analysis of Primary Endpoint-Trial 1 (ITT population)

Subgroup IBSRELA
n/N (%)
Placebo
n/N (%)
Difference (95% CI)
Sex
Women 91/240 (37.9%) 62/247 (25.1%) 12.8% (4.6%, 21.0%)
Men 16/53 (30.2%) 9/53 (17.0%) 13.2% (-3.8%, 29.2%)
Race
White 69/185 (37.3%) 47/192 (24.5%) 12.8% (3.6%, 22.1%)
Black or African American 35/92 (38.0%) 22/92 (23.9%) 14.1% (0.9%, 27.3%)
Asian 1/12 (8.3%) 2/9 (22.2%) -13.9% (-45.2%, 17.5%)
Age Category      
<65 years 101/271 (37.3%) 65/273 (23.8%) 13.5% (5.8%, 21.1%)
≥65 years 6/22 (27.3%) 6/27 (22.2%) 5.1% (- 19.3%, 29.4%)

Table 4. Subgroup Analysis of Primary Endpoint-Trial 2 (ITT population)

Subgroup IBSRELA
n/N (%)
Placebo
n/N (%)
Difference (95% CI)
Sex
Women 88/244 (36.1%) 79/249 (31.7%) 4.3% (-4.0%, 12.7%)
Men 16/63 (25.4%) 9/50 (18.0%) 7.4% (-7.7%, 22.5%)
Race
White 55/201 (27.4%) 28/186 (15.1%) 12.3% (4.3%, 20.3%)
Black or African American 26/88 (29.6%) 24/100 (24.0%) 5.6% (-7.1%, 18.2%)
Asian 0/10 (0%) 1/4 (25%) -25% (-67.4%, 17.4%)
Age Category
<65 years 71/279 (25.5%) 52/277 (18.8%) 6.7% (- 0.2%, 13.6%)
≥65 years 12/28 (42.9%) 4/22 (18.2%) 24.7% (0.3%, 49.1%)

FDA Review

What are the possible side effects?

IBSRELA may cause serious dehydration in children. It should not be given to children younger than 6 years of age and avoided in children 6 to 12 years of age.

The most common side effects of IBSRELA are diarrhea, which sometimes may be severe, abdominal distension, excessive gas and dizziness.

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions for the Trial 1.

Table 5. Most Common Adverse Reactions* in Patients with IBS-C in Trial 1 (26 Weeks)

Adverse Reactions IBSRELA
N=293
%
Placebo
N=300
%
Diarrhea 16 4
Abdominal Distension 3 <1
Flatulence 3 1
Dizziness 2 <1

* Reported in at least 2% of patients in IBSRELA-treated patients and at an incidence greater than placebo

In Trial 2 (610 patients: 309 IBSRELA-treated and 301 placebo-treated) the most common adverse reactions were diarrhea (15% with IBSRELA vs 2% with placebo) and abdominal distension (2% with IBSRELA vs 0% with placebo).

Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The majority of patients in the trials were women. The occurrence of side effects was similar in men and women.
  • Race: The occurrence of side effects was similar in different races.
  • Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Per trial analyses of subgroup treatment emergent adverse events (TEAEs) and most common adverse reaction (diarrhea) are presented below.

Table 6. Subgroup Analysis of Patients with Any TEAEs and Diarrhea -Trial 1 (safety population)

Demographic Subgroup IBSRELA
N=293
Placebo N=300 Any TEAE Risk Difference
% (95% CI)
Diarrhea Risk Difference
% (95% CI)
IBSRELA
N=146
n (%)
Placebo
N=109
n (%)
ISBRELA N=48
n (%)
Placebo
(N=11)
n (%)
Sex
Men 53 53 22 (42%) 1 (32%) 10 (-8,28) 7 (13%) 0 (0%) 13 (8,18)
Women 240 247 124 (52%) 108 (44%) 8 (-1,17) 41 (17%) 11 (4.5%) 12.5 (7.5,17)
Race
White 185 192 92 (50%) 77 (40%) 10 (0,20) 39 (21%) 8 (4.2%) 17 (10,24)
Black or African American 92 92 49 (53%) 42 (46%) 7 (-7,21) 8 (8.7%) 3 (3.3) 5.4 (-1.6,12)
Asian 12 9 3 (25%) 4 (44%) -19 (-60,22) 0 (0%) 0 (0%) 0
American Indian or Alaska Native 1 0 0 (0%) 0 (0%) 0 0 (0%) 0 (0%) 0
All Other 3 7 2 (67%) 2 (29%) 38 (-25,101) 1 (33%) 0 (0%) 33 (-20,86)
Age
≤65 years 273 276 136 (50%) 115(42%) 8 (0,16) 46 (17%) 11 (4.0%) 13 (8,18)
>65 years 20 24 10 (50%) 10 (42%) 8 (-21,37) 2 (10%) 0 (0%) 10 (-3,23)

Table 7. Subgroup Analysis of Patients with Any TEAEs and Diarrhea -Trial 2 (safety population)

Demographic Subgroup IBSRELA
N=309
Placebo
N=301
Any TEAE Risk Difference
% (95% CI)
Diarrhea Risk Difference
% (95% CI)
ISBRELA
N=188
n (%)
Placebo
N=94
n (%)
IBSRELA
N=80
n (%)
Placebo
N=5
n (%)
Sex
Men 64 50 24 (38%) 11 (22%) 16 (-1,33) 8 (12%) 0 (0%) 12 (4,20)
Women 245 251 164 (67%) 83 (33%) 34 (26,42) 72 (29%) 5 (2%) 27 (21,31)
Race
White 202 188 125 (62%) 54 (29%) 33 (24,42) 56 (29%) 2 (1.1%) 28 (22,34)
Black or African American 89 100 53 (60%) 34 (34%) 26 (12,40) 19 (21%) 2 (2%) 19 (10,28)
Asian 10 4 5 (50%) 2 (50%) 0 1 (10%) 1 (25%) -15 (-61,31)
American Indian or Alaska Native 0 2 0 (0%) 0 (0%) 0 0 (0%) 0 (0%) 0
All Other 8 7 5 (62%) 4 (57%) 5( -45,55) 0 (0%) 0 (0%) 0
Age
≤65 years 284 281 175 (62%) 90 (32%) 30 (22,38) 74 (26%) 5 (1.8%) 24 (19,29)
>65 years 25 20 13 (52%) 4 (20%) 32 (6,58) 6 (24%) 0 (0%) 24 (7,41)

Adapted from FDA Review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved IBSRELA based primarily on evidence from two clinical trials Trial 1(NCT 02686138) and Trial 2(NCT 02621892) of 1199 patients 18 to 75 years of age with IBS-C. The trials were conducted at 214 sites in the United States.

Figure 1 summarizes how many men and women were in the clinical trials used to evaluate the benefit of IBSRELA.

Figure 1. Baseline Demographics by Sex (efficacy population)

Pie chart summarizing how many men and women were in the clinical trial. In total, 219 men (18%) and 980 women (82%) participated in the clinical trial.

Clinical Trial Data

Figure 2 and Table 1 summarize the percentage of patients by race in the clinical trials used to evaluate the benefit of IBSRELA.

Figure 2. Baseline Demographics by Race (efficacy population)

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 764 White (64%), 372 Black or African American (31%), 35 Asian (3%), 15 Multiple (1%), 13 and Other (1%)

Clinical Trial Data

Table 1. Demographics of Efficacy Trials by Race (efficacy population)

Race Number of Patients Percentage
White 764 64
Black or African American 372 31
Asian 35 3
American Indian or Alaska Native 3 Less than 1
Multiple 15 1
Other/Unknown 10 1

Figure 3. Baseline Demographics by Age (efficacy population)

Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total, 1100 patients were less than 40 years old (13%), 2100 patients were 40 to 64 years old (67%) and 639 patients were 65 years and older (20%).

Clinical Trial Data

Who participated in the trials?

The table below summarizes demographics for the efficacy (ITT) population.

Table 8. Demographic of ITT Population

Demographic Parameters Trial 1 Trial 2 Total
(N=1199)
n (%)
IBSRELA
(N=293)
n (%)
Placebo
(N=300)
n (%)
IBSRELA
(N=307)
n (%)
Placebo
(N=299)
n (%)
Sex
Men 53 (18.1) 53 (17.7) 63 (20.5) 50 (16.7) 219 (18.3)
Women 240 (81.9) 247 (82.3) 244 (79.5) 249 (83.3) 980 (81.7)
Race
White 185 (63.1) 192 (64) 201 (65.5) 186 (62.2) 764 (63.7)
Black or African American 92 (31.4) 92 (30.7) 88 (28.7) 100 (33.4) 372 (31)
Asian 12 (4.1) 9 (3) 10 (3.3) 4 (1.3) 35 (2.9)
American Indian or
Alaska Native
1 (0.3) 0 0 2 (0.7) 3 (0.3)
Multiple 1 (0.3) 3 (1) 6 (2) 5 (1.7) 15 (1.3)
Other/Unknown 2 (0.6) 4 (1.3) 2 (0.7) 2 (0.7) 10 (0.8)
Age
Median (years) 46 44 45 45 45
Min, Max (years) 18, 74 18,75 18, 73 18,75 18,75
Age Category
<65 years 271 (92.5) 273 (91) 279 (90.9) 277 (92.6) 1100 (91.7)
>=65 years 22 (7.5) 27 (9) 28 (9.1) 22 (7.4) 99 (8.3)
Ethnicity
Hispanic or Latino 77 (26.3) 78 (26) 98 (31.9) 83 (27.8) 336 (28)
Not Hispanic or Latino 216 (73.7) 222 (74) 209 (68.1) 216 (72.2) 863 (82)
Region
United States 293 (100) 300 (100) 299 (100) 307 (100) 1199 (100)

Clinical Trial Data

How were the trials designed?

There were two trials that evaluated the benefit and side effects of IBSRELA. In each trial, patients were randomly assigned to receive either IBSRELA or placebo two times daily for at least 12 weeks. Neither the patients nor the health care providers knew which treatment was being given. After these 12 weeks of treatment, patients in Trial 1 continued same trial design for an additional 14 weeks, and patients in Trial 2 entered a different trial design called Randomized Withdrawal for 4 weeks, where some patients continued to receive IBSRELA, and others were switched to placebo, in a blinded fashion.

In both trials, patients used diaries to record the degree of abdominal pain and stool frequency. The benefit of IBSRELA was assessed by improvements in abdominal pain and complete spontaneous bowel movements in comparison to placebo.

How were the trials designed?

Two randomized, multi-center, double-blind, placebo-controlled trials were conducted to assess the efficacy and safety of IBSRELA in comparison to placebo in adult patients with IBS-C.

The trial designs were identical through the first 12 weeks of treatment, and thereafter differed in that Trial 1 continued for an additional 14 weeks of treatment (26 weeks double-blind treatment), whereas Trial 2 included a 4-week randomized withdrawal (RW) period.

Efficacy of IBSRELA was assessed using responder analyses based on daily diary entries.

In both trials, the primary endpoint was the proportion of responders, where a responder was defined as a patient achieving

  • at least a 30% reduction in the weekly average of abdominal pain score compared with baseline, and
  • an increase of at least 1 complete spontaneous bowel movement in the same week for at least 6 of the first 12 weeks of treatment.

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.

PRESCRIBING INFORMATION

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