Trial Outcomes & Findings for Telotristat Ethyl for the Treatment of Carcinoid Heart Disease in Patients With Metastatic Neuroendocrine Tumor (NCT NCT04810091)
NCT ID: NCT04810091
Last Updated: 2026-03-09
Results Overview
Percent change in N-terminal pro B-type natriuretic peptide (NT-proBNP) from baseline to 6 months defined as (NTproBNP at 6 month - NTproBNP at baseline)/(NTproBNP at baseline)\*100
ACTIVE_NOT_RECRUITING
PHASE3
79 participants
Baseline and at 6 months
2026-03-09
Participant Flow
Of the 79 participants who consented and enrolled in the study, 6 withdrew before arm assignment. These 6 participants were not randomized and were excluded from the study. The remaining 73 participants were randomized to one of two arms.
Participant milestones
| Measure |
Placebo + SSA
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Overall Study
STARTED
|
37
|
36
|
|
Overall Study
Randomized
|
37
|
36
|
|
Overall Study
Treated
|
35
|
32
|
|
Overall Study
3 Month Follow-up
|
29
|
29
|
|
Overall Study
COMPLETED
|
27
|
26
|
|
Overall Study
NOT COMPLETED
|
10
|
10
|
Reasons for withdrawal
| Measure |
Placebo + SSA
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Physician Decision
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
4
|
2
|
|
Overall Study
Ineligible
|
0
|
1
|
|
Overall Study
Non-compliance
|
0
|
1
|
|
Overall Study
Prescribed Xermelo by local oncologist
|
1
|
0
|
|
Overall Study
Progressive disease
|
0
|
1
|
Baseline Characteristics
Telotristat Ethyl for the Treatment of Carcinoid Heart Disease in Patients With Metastatic Neuroendocrine Tumor
Baseline characteristics by cohort
| Measure |
Placebo + SSA
n=37 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=36 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
Total
n=73 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=68 Participants
|
0 Participants
n=69 Participants
|
0 Participants
n=137 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=68 Participants
|
0 Participants
n=69 Participants
|
0 Participants
n=137 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=68 Participants
|
20 Participants
n=69 Participants
|
42 Participants
n=137 Participants
|
|
Age, Categorical
>=65 years
|
15 Participants
n=68 Participants
|
16 Participants
n=69 Participants
|
31 Participants
n=137 Participants
|
|
Age, Continuous
|
63.4 years
STANDARD_DEVIATION 11.6 • n=68 Participants
|
59.2 years
STANDARD_DEVIATION 14.4 • n=69 Participants
|
61.4 years
STANDARD_DEVIATION 12.6 • n=137 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=68 Participants
|
16 Participants
n=69 Participants
|
30 Participants
n=137 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=68 Participants
|
20 Participants
n=69 Participants
|
43 Participants
n=137 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=68 Participants
|
6 Participants
n=69 Participants
|
10 Participants
n=137 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
30 Participants
n=68 Participants
|
30 Participants
n=69 Participants
|
60 Participants
n=137 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=68 Participants
|
0 Participants
n=69 Participants
|
3 Participants
n=137 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=68 Participants
|
0 Participants
n=69 Participants
|
0 Participants
n=137 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=68 Participants
|
1 Participants
n=69 Participants
|
1 Participants
n=137 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=68 Participants
|
4 Participants
n=69 Participants
|
8 Participants
n=137 Participants
|
|
Race (NIH/OMB)
White
|
32 Participants
n=68 Participants
|
29 Participants
n=69 Participants
|
61 Participants
n=137 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=68 Participants
|
0 Participants
n=69 Participants
|
0 Participants
n=137 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=68 Participants
|
2 Participants
n=69 Participants
|
3 Participants
n=137 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=68 Participants
|
36 participants
n=69 Participants
|
73 participants
n=137 Participants
|
PRIMARY outcome
Timeframe: Baseline and at 6 monthsPopulation: Patients who had NTproBNP at both baseline and 6 months
Percent change in N-terminal pro B-type natriuretic peptide (NT-proBNP) from baseline to 6 months defined as (NTproBNP at 6 month - NTproBNP at baseline)/(NTproBNP at baseline)\*100
Outcome measures
| Measure |
Placebo + SSA
n=27 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=26 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Percent Change in NTproBNP at 6 Months Visit From Baseline
|
-9.1 Percent change from baseline
Interval -32.4 to 14.3
|
1.4 Percent change from baseline
Interval -32.4 to 53.8
|
SECONDARY outcome
Timeframe: Baseline and 3 month follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 25 completed the 6MWT at both baseline and 3 months. In the Xermelo + SSA arm, all 29 participants who completed 3-month follow-up also completed the 6MWT at both baseline and at 3 months.
Change in functional capacity from baseline to 3-month visit, assessed by a 6-minute walk test (6MWT), where 6MWT is defined as the distance walked in 6 minutes, and the change is calculated as: 6MWT at 3 months minus 6MWT at baseline
Outcome measures
| Measure |
Placebo + SSA
n=25 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=29 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in 6MWT at 3 Month Visit
|
0 meters
Interval -35.0 to 45.0
|
8 meters
Interval -25.0 to 64.0
|
SECONDARY outcome
Timeframe: Baseline and 6 month follow-upPopulation: Of the 27 participants who completed 6-month follow-up in the Placebo + SSA arm, 26 participants completed 6MWT at both baseline and at 6 months. All 26 participants who completed 6-month follow-up in the Xermelo + SSA arm completed the 6MWT at both baseline and 6 months.
Change in functional capacity from baseline to 6-month visit, assessed by a 6-minute walk test (6MWT), where 6MWT is defined as the distance walked in 6 minutes, and the change is calculated as: 6MWT at 6 months minus 6MWT at baseline
Outcome measures
| Measure |
Placebo + SSA
n=26 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=26 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in 6MWT at 6 Month Visit
|
-14 meters
Interval -63.0 to 39.0
|
25.5 meters
Interval -27.0 to 67.0
|
SECONDARY outcome
Timeframe: Baseline and 3 month follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 7 completed CVHD evaluations at both baseline and 3 months. In the Xermelo + SSA arm, 5 of the 29 participants who completed 3-month follow-up completed CVHD evaluations at both baseline and 3 months.
The Carcinoid Valvular Heart disease (CVHD) % score at 3 months minus CVHD % score at baseline. CVHD score was determined by 1) tricuspid valve appearance, 2) tricuspid regurgitation severity by either spectral pulsed wave or color dopplet flow mapping, 3) pulmonary stenosis severity by spectral pulsed or continuous wave Doppler, and 4) pulmonary insufficiency severity by color Doppler. CVHD % score was calculated as total points assigned across four echo parameters (specified above 1-4)) divided by the maximum possible points (14) and multiplied by 100. The CVHD % score ranges from 0% to 100%, with higher values indicating more severe disease. The change in CVHD % score from baseline to 3 months reflects disease progression or improvement: a positive change indicates worsening valvular involvement, a negative change indicates improvement, and zero indicates stability.
Outcome measures
| Measure |
Placebo + SSA
n=7 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=5 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in CVHD % Score From Baseline to 3 Month Visit
|
0 Scores on a scale
Interval -7.0 to 0.0
|
0 Scores on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 6 month follow-upPopulation: Of the 27 participants who completed 6-month follow-up in the Placebo + SSA arm, 24 participants completed CVHD evaluations at both baseline and 6 months. In the Xermelo + SSA arm, 23 of the 26 participants who completed 6-month follow-up completed CVHD evaluation at both baseline and at 6 months. The values reported represent the median values for change in CVHD score for each Arm, and do not represent non-meaningful placeholders.
The Carcinoid Valvular Heart disease (CVHD) % score at 6 months minus CVHD % score at baseline. CVHD score was determined by 1) tricuspid valve appearance, 2) tricuspid regurgitation severity by either spectral pulsed wave or color dopplet flow mapping, 3) pulmonary stenosis severity by spectral pulsed or continuous wave Doppler, and 4) pulmonary insufficiency severity by color Doppler. CVHD % score was calculated as total points assigned across four echo parameters divided by the maximum possible points (14) and multiplied by 100. The CVHD % score ranges from 0% to 100%, with higher values indicating more severe disease. The change in CVHD % score from baseline to 6 months reflects disease progression or improvement: a positive change indicates worsening valvular involvement, a negative change indicates improvement, and zero indicates stability.
Outcome measures
| Measure |
Placebo + SSA
n=24 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=23 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in CVHD Score From Baseline to 6 Month Visit
|
0 Scores on a scale
Interval 0.0 to 0.0
|
0 Scores on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 3 month follow-upPopulation: Of the 29 participants who completed 3 months follow-up in the Placebo + SSA arm, 3 completed strain RV evaluations at both baseline and 3 months. In the Xermelo + SSA arm, 7 of the 29 participants who completed 3-month follow-up completed strain RV evaluations at both baseline and at 3 months.
Percentage of participants with a significant change in right ventricular global longitudinal strain (strain-RV) from baseline to 3 months. A significant change is defined as an 15% or more change (increase or decrease) from baseline to 3 months. The Exact 2-sided 95% CI is based on the observed proportion of participants.
Outcome measures
| Measure |
Placebo + SSA
n=3 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=7 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Percentage of Participants With Significant Change in Strain-RV From Baseline at 3 Months
|
33.3 Percentage of Participants
Interval 0.8 to 90.6
|
42.9 Percentage of Participants
Interval 9.9 to 81.6
|
SECONDARY outcome
Timeframe: Baseline and 6 month follow-upPopulation: Of the 27 participants who completed 6-month follow-up in the Placebo + SSA arm, 7 completed strain RV evaluations at both baseline and 6 months. In the Xermelo + SSA arm, 5 of the 26 participants who completed 6-month follow-up completed strain RV evaluations at both baseline and 6 months.
Percentage of participants with a significant change in right ventricular global longitudinal strain (strain-RV) from baseline to 6 months. A significant change is defined as an 15% or more change (increase or decrease) from baseline to 6 months. The Exact 2-sided 95% CI is based on the observed proportion of participants.
Outcome measures
| Measure |
Placebo + SSA
n=7 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=5 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Percentage of Participants With Significant Change in Strain-RV From Baseline at 6 Months
|
42.9 Percentage of Participants
Interval 9.9 to 81.6
|
40 Percentage of Participants
Interval 5.3 to 85.3
|
SECONDARY outcome
Timeframe: Baseline and 3 month follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 7 participants completed strain LV evaluations at both baseline and 3 months. In the Xermelo + SSA arm, 7 of the 29 participants who completed 3-month follow-up completed strain LV evaluations at both baseline and 3 months.
Percentage of participants with a significant change in left ventricular global longitudinal strain (strain-LV) from baseline to 3 months. A significant change is defined as an 15% or more change (increase or decrease) from baseline to 3 months. The Exact 2-sided 95% CI is based on the observed proportion of participants.
Outcome measures
| Measure |
Placebo + SSA
n=7 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=7 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Percentage of Participants With Significant Change in Strain-LV From Baseline at 3 Months
|
14.3 Percentage of Participants
Interval 0.4 to 57.9
|
28.6 Percentage of Participants
Interval 3.7 to 71.0
|
SECONDARY outcome
Timeframe: Baseline and 6 month follow-upPercentage of participants with a significant change in left ventricular global longitudinal strain (strain-LV) from baseline to 6 months. A significant change is defined as an 15% or more change (increase or decrease) from baseline to 6 months. The Exact 2-sided 95% CI is based on the observed proportion of participants.
Outcome measures
| Measure |
Placebo + SSA
n=15 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=16 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Percentage of Participants With Significant Change in Strain-LV From Baseline at 6 Months
|
13.3 Percentage of Participants
Interval 1.7 to 40.5
|
12.5 Percentage of Participants
Interval 1.6 to 38.4
|
SECONDARY outcome
Timeframe: 3 month follow-upPopulation: Among 29 who completed 3 months follow-up in the Placebo + SSA arm, 5 participants completed TAPSE evaluations at both baseline and at 3 months. In the Xermelo + SSA arm, 7 of the 29 participants who completed TAPSE evaluations at both baseline and at 3 months.
Percentage of participants with a normal Tricuspid Annular Plane Systolic Excursion (TAPSE) at 3 months, where TAPSE ≥1.6cm is defined as normal. The Exact 2-sided 95% CI is based on the observed proportion of participants.
Outcome measures
| Measure |
Placebo + SSA
n=5 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=7 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Percentage of Participants With Normal TAPSE at 3 Months
|
100 Percentage of Participants
Interval 47.8 to 100.0
|
86 Percentage of Participants
Interval 42.1 to 99.6
|
SECONDARY outcome
Timeframe: 6 month follow-upPopulation: Of the 27 participants who completed 6-month follow-up in the Placebo + SSA arm, 21 completed TAPSE evaluations at both baseline and 6 months. In Xermelo + SSA arm, 20 of the 26 who completed 6-month follow-up ccompleted TAPSE evaluation at both baseline and 6 months.
Percentage of participants with a normal Tricuspid Annular Plane Systolic Excursion (TAPSE) at 6 months, where TAPSE ≥1.6cm is defined as normal. The Exact 2-sided 95% CI is based on the observed proportion of participants.
Outcome measures
| Measure |
Placebo + SSA
n=21 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=20 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Percentage of Participants With Normal TAPSE at 6 Months
|
100 Percentage of Participants
Interval 83.9 to 100.0
|
95 Percentage of Participants
Interval 75.1 to 99.9
|
SECONDARY outcome
Timeframe: Baseline and 3 month follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 26 completed 5HIAA evaluations at both baseline and 3 months. In Xermelo + SSA arm, all 29 who completed 3-month follow-up completed 5HIAA evaluations at both baseline and 3 months.
Change in plasma 5HIAA (5-Hydroxyindoleacetic acid) level from baseline to 3 months. The change is calculated as: 5HIAA at 3 months minus 5HIAA at baseline
Outcome measures
| Measure |
Placebo + SSA
n=26 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=29 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in 5HIAA From Baseline to 3 Months
|
-0.9 ng/mL
Interval -4.2 to 6.6
|
-55.3 ng/mL
Interval -118.2 to -28.6
|
SECONDARY outcome
Timeframe: Baseline and 6 month follow-upChange in 5HIAA measurement from baseline to 6 months
Outcome measures
| Measure |
Placebo + SSA
n=26 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=26 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in 5HIAA From Baseline to 6 Months
|
0.1 ng/mL
Interval -1.9 to 7.3
|
-56.4 ng/mL
Interval -104.4 to -18.6
|
SECONDARY outcome
Timeframe: Baseline and 3 months follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 25 completed troponin evaluation at both baseline and 3 months. In the Xermelo + SSA arm, 25 of the 29 who completed 3-month completed troponin evaluation at both baseline and 3 months.
Change in troponin level from baseline to 3 months, calculated as: troponine at 3 months minus troponin at baseline
Outcome measures
| Measure |
Placebo + SSA
n=25 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=25 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in Troponin From Baseline to 3 Months
|
0 ng/L
Interval -1.0 to 2.0
|
0 ng/L
Interval -2.0 to 1.0
|
SECONDARY outcome
Timeframe: Baseline and 6 months follow-upPopulation: Of the 27 participants who completed 6-month follow-up in the Placebo + SSA arm, 26 completed troponin evaluation at both baseline and 6 months. In the Xermelo + SSA arm, 25 of the 26 who completed 6-month follow-up completed troponin evaluation at both baseline and at 6 months.
Change in troponin level from baseline to 6 months, calculated as: troponine at 6 months minus troponin at baseline
Outcome measures
| Measure |
Placebo + SSA
n=26 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=25 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in Troponin From Baseline to 6 Months
|
0 ng/L
Interval -1.0 to 1.0
|
0 ng/L
Interval -2.0 to 1.0
|
SECONDARY outcome
Timeframe: Baseline and 3 months follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 27 completed MDASI core symptom evaluation at both baseline and 3 months. In the Xermelo + SSA arm, 28 of the 29 participants who completed 3-month follow-up completed MDASI core symptom evaluation at both baseline and 3 months.
Change in MD Anderson Symptom Inventory (MDASI) mean core symptom score from baseline to 3 months. The MDASI mean core symptom score is calculated as the mean of 13 core symptom items, each ranged from 0 ( "not present") to 10 being ("as bad as you can imagine"), with the higher scores indicating worse symptoms. The change is computed as: score at 3 months minus score at baseline
Outcome measures
| Measure |
Placebo + SSA
n=27 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=28 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in MDASI Mean Core Symptom Score From Baseline to 3 Months
|
-0.2 Scores on a scale
Interval -0.4 to 0.4
|
0.1 Scores on a scale
Interval -0.2 to 0.3
|
SECONDARY outcome
Timeframe: Baseline and 6 months follow-upPopulation: All 27 participants who completed 6-month follow-up in the Placebo + SSA arm completed MDASI core symptom evaluation at both baseline and 6 months. In the Xermelo + SSA arm, 25 of the 26 participants who completed 6-month follow-up completed MDASI core symptom evaluation at both baseline and 6 months.
Change in MD Anderson Symptom Inventory (MDASI) mean core symptom score from baseline to 6 months. The MDASI mean core symptom score is calculated as the mean of 13 core symptom items, each ranged from 0 ( "not present") to 10 being ("as bad as you can imagine"), with the higher scores indicating worse symptoms. The change is computed as: score at 6 months minus score at baseline
Outcome measures
| Measure |
Placebo + SSA
n=27 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=25 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in Core Symptom Score From Baseline to 6 Months
|
0 Scores on a scale
Interval -0.3 to 0.4
|
0 Scores on a scale
Interval -0.3 to 0.2
|
SECONDARY outcome
Timeframe: Baseline and 3 months follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 27 completed MDASI total symptom evaluation at both baseline and 3 months. In the Xermelo + SSA arm, all 28 participants who completed 3-month follow-up completed MDASI total symptom evaluation at both baseline and 3 months.
Change in MD Anderson Symptom Inventory (MDASI) mean total symptom score from baseline to 3 months. The MDASI mean total symptom score is calculated as the mean symptom severity of 21 symptom items (13 core symptom items and 8 additional symptom items), each ranged from 0 ( "not present") to 10 being ("as bad as you can imagine), with the higher scores indicating worse symptoms. The change is computed as: score at 3 months minus score at baseline
Outcome measures
| Measure |
Placebo + SSA
n=27 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=28 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in MDASI Mean Total Symptom Score From Baseline to 3 Months
|
0 points
Interval -0.3 to 0.5
|
0 points
Interval -0.2 to 0.2
|
SECONDARY outcome
Timeframe: Baseline and 6 months follow-upPopulation: All 27 participants who completed 6-month follow-up in the Placebo + SSA arm completed MDASI total symptom evaluation at both baseline and 6 months. In the Xermelo + SSA arm, 25 of the 26 participants who completed 6-month follow-up completed MDASI total symptom evaluation at both baseline and 6 months.
Change in MD Anderson Symptom Inventory (MDASI) mean total symptom score from baseline to 6 months. The MDASI mean total symptom score is calculated as the mean symptom severity of 21 symptom items (13 core symptom items and 8 additional symptom items), each ranged from 0 ( "not present") to 10 being ("as bad as you can imagine), with the higher scores indicating worse symptoms. The change is computed as: score at 6 months minus score at baseline
Outcome measures
| Measure |
Placebo + SSA
n=27 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=25 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in MDASI Mean Total Symptom Score From Baseline to 6 Months
|
-0.1 Scores on a scale
Interval -0.2 to 0.2
|
0 Scores on a scale
Interval -0.4 to 0.3
|
SECONDARY outcome
Timeframe: Baseline and 3 months follow-upPopulation: Of the 29 participants who completed 3-month follow-up in the Placebo + SSA arm, 26 completed MDASI interference evaluation at both baseline and 3 months. In the Xermelo + SSA arm, 28 of the 29 participants who completed 3-month follow-up completed MDASI interference evaluation at both baseline and 3 months.
Change in MD Anderson Symptom Inventory (MDASI) mean interference score from baseline to 3 months. The MDASI mean interference score is calculated as the mean of 6 interference items, each ranged from 0 ( "not present") to 10 being ("as bad as you can imagine"), with the higher scores indicating worse interference. The change is computed as: score at 3 months minus score at baseline
Outcome measures
| Measure |
Placebo + SSA
n=26 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=28 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in MDASI Mean Interference Score From Baseline to 3 Months
|
0 Scores on a scale
Interval -0.3 to 0.8
|
0 Scores on a scale
Interval -0.4 to 0.1
|
SECONDARY outcome
Timeframe: Baseline and 6 months follow-upPopulation: Of the 27 participants who completed 6-month follow-up in the Placebo + SSA arm, 26 completed MDASI interferemce evaluation at both baseline and 6 months. In the Xermelo + SSA arm, 24 of the 26 who completed 6-month follow-up completed MDASI interference evaluation at both baseline and 6 months.
Change in MD Anderson Symptom Inventory (MDASI) mean interference score from baseline to 6 months. The MDASI mean interference score is calculated as the mean of 6 interference items, each ranged from 0 ( "not present") to 10 being ("as bad as you can imagine"), with the higher scores indicating worse interference. The change is computed as: score at 6 months minus score at baseline
Outcome measures
| Measure |
Placebo + SSA
n=26 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=24 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Change in Interference Score From Baseline to 6 Months
|
0 Scores on a scale
Interval -0.3 to 0.5
|
0 Scores on a scale
Interval -0.5 to 0.0
|
SECONDARY outcome
Timeframe: Baseline, 3 months follow-up, 6 months follow-upPopulation: Those who were treated: 35 in placebo + SSA and 32 in Xermelo + SSA
Percentage of participants classified as compliant (compliance≥70%) during the study. Compliance is calculated as the total number of pills taken divided by the toal number of pills dispensed while the patient was on the study. Participants with compliance≥70% are considered compliant; otherwise, not compliant.
Outcome measures
| Measure |
Placebo + SSA
n=35 Participants
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=32 Participants
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Compliance>=70% While the Patients Were in the Study
|
74.3 Percentage of Participants
Interval 56.7 to 87.5
|
87.5 Percentage of Participants
Interval 71.0 to 96.5
|
Adverse Events
Placebo + SSA
Xermelo + SSA
Serious adverse events
| Measure |
Placebo + SSA
n=35 participants at risk
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=32 participants at risk
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Gastrointestinal disorders
Ascites (death)
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
0.00%
0/32 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
General disorders
Cataract
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
0.00%
0/32 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/35 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/35 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Cardiac disorders
Ejection fraction decreased
|
0.00%
0/35 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
General disorders
Fatigue
|
0.00%
0/35 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/35 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Nervous system disorders
Presyncope
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
0.00%
0/32 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Nervous system disorders
Syncope
|
0.00%
0/35 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
Other adverse events
| Measure |
Placebo + SSA
n=35 participants at risk
Placebo-matching telotristat ethyl tablet TID + stable-dose somatostatin analog (SSA) therapy
|
Xermelo + SSA
n=32 participants at risk
Telotristat ethyl 500 mg po TID + stable-dose somatostatin analog (SSA)
|
|---|---|---|
|
Investigations
Blood lactate dehydrogenase increased
|
5.7%
2/35 • Number of events 2 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
6.2%
2/32 • Number of events 2 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Gastrointestinal disorders
Nausea
|
17.1%
6/35 • Number of events 11 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
21.9%
7/32 • Number of events 8 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Gastrointestinal disorders
Constipation
|
14.3%
5/35 • Number of events 6 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
25.0%
8/32 • Number of events 8 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Investigations
Alkaline phosphtase increased
|
8.6%
3/35 • Number of events 4 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
25.0%
8/32 • Number of events 8 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
General disorders
Fatigue
|
11.4%
4/35 • Number of events 6 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
15.6%
5/32 • Number of events 5 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Nervous system disorders
Headache
|
11.4%
4/35 • Number of events 5 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
18.8%
6/32 • Number of events 6 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Blood and lymphatic system disorders
Anemia
|
11.4%
4/35 • Number of events 4 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
15.6%
5/32 • Number of events 5 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Renal and urinary disorders
Creatinine increased
|
22.9%
8/35 • Number of events 8 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
14.3%
5/35 • Number of events 5 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
9.4%
3/32 • Number of events 3 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Cardiac disorders
Heart failure
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
21.9%
7/32 • Number of events 7 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
8.6%
3/35 • Number of events 3 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
12.5%
4/32 • Number of events 5 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Investigations
Cardiac troponin T increased
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
18.8%
6/32 • Number of events 6 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Gastrointestinal disorders
Abdominal pain
|
11.4%
4/35 • Number of events 5 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Gastrointestinal disorders
Bloating
|
11.4%
4/35 • Number of events 5 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
General disorders
Edema limbs
|
17.1%
6/35 • Number of events 6 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
0.00%
0/32 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Metabolism and nutrition disorders
Anorexia
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
9.4%
3/32 • Number of events 4 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Cardiac disorders
Chest pain - cardiac
|
8.6%
3/35 • Number of events 4 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Renal and urinary disorders
Chronic kidney disease
|
8.6%
3/35 • Number of events 3 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
6.2%
2/32 • Number of events 2 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Gastrointestinal disorders
Diarrhea
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
9.4%
3/32 • Number of events 4 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Investigations
Aspartate aminotransferase increased
|
8.6%
3/35 • Number of events 3 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
3.1%
1/32 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
31.4%
11/35 • Number of events 13 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
62.5%
20/32 • Number of events 21 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Nervous system disorders
Dizziness
|
2.9%
1/35 • Number of events 1 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
6.2%
2/32 • Number of events 3 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
|
Vascular disorders
Flushing
|
5.7%
2/35 • Number of events 2 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
6.2%
2/32 • Number of events 2 • Adverse events were monitored from baseline throughout the follow-up period (3-month and 6-month follow-up visits) and for up to 30 days after the last dose of the study drug, with the treatment period planned for 6-months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place