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An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With Early-Stage HER2+ Breast Cancer Treated With Neratinib and Loperamide

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02400476
Recruitment Status : Completed
First Posted : March 27, 2015
Results First Posted : May 6, 2022
Last Update Posted : May 6, 2022
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Early Stage HER2+ Breast Cancer
Interventions Drug: Neratinib
Drug: Loperamide
Drug: Colestipol
Drug: Budesonide
Enrollment 563
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Hide Arm/Group Description

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.

Neratinib

Loperamide

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.

Neratinib

Loperamide

Budesonide: 9 mg extended release tablets once daily with or without food for 28 days

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.

Neratinib

Loperamide

160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.

Neratinib

Loperamide

Period Title: Overall Study
Started 137 64 136 104 60 62
Completed 76 52 95 74 45 46
Not Completed 61 12 41 30 15 16
Reason Not Completed
Adverse Event             57             10             22             19             5             8
Withdrawal by Subject             4             1             12             7             5             5
Lost to Follow-up             0             0             0             1             3             1
Physician Decision             0             0             1             1             0             1
Other, Disease Progression             0             1             2             1             2             1
Other, Decreased Quality of Life             0             0             2             0             0             0
Other, Noncompliance to Protocol Requirements             0             0             2             1             0             0
Arm/Group Title Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2 Total
Hide Arm/Group Description

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.

Neratinib

Loperamide

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.

Neratinib

Loperamide

Budesonide: 9 mg extended release tablets once daily with or without food for 28 days

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.

Neratinib

Loperamide

160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.

Neratinib

Loperamide

Total of all reporting groups
Overall Number of Baseline Participants 137 64 136 104 60 62 563
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 137 participants 64 participants 136 participants 104 participants 60 participants 62 participants 563 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
116
  84.7%
58
  90.6%
117
  86.0%
93
  89.4%
51
  85.0%
52
  83.9%
487
  86.5%
>=65 years
21
  15.3%
6
   9.4%
19
  14.0%
11
  10.6%
9
  15.0%
10
  16.1%
76
  13.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 137 participants 64 participants 136 participants 104 participants 60 participants 62 participants 563 participants
53.39  (11.06) 49.11  (10.55) 52.49  (11.08) 51.94  (10.23) 51.90  (10.71) 53.82  (10.15) 52.31  (10.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 137 participants 64 participants 136 participants 104 participants 60 participants 62 participants 563 participants
Female
137
 100.0%
64
 100.0%
133
  97.8%
104
 100.0%
60
 100.0%
62
 100.0%
560
  99.5%
Male
0
   0.0%
0
   0.0%
3
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
3
   0.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 137 participants 64 participants 136 participants 104 participants 60 participants 62 participants 563 participants
White
113
  82.5%
50
  78.1%
96
  70.6%
80
  76.9%
53
  88.3%
52
  83.9%
444
  78.9%
Black or African American
11
   8.0%
5
   7.8%
9
   6.6%
8
   7.7%
1
   1.7%
2
   3.2%
36
   6.4%
Asian
8
   5.8%
4
   6.3%
13
   9.6%
9
   8.7%
3
   5.0%
1
   1.6%
38
   6.7%
American Indian or Alaska Native
1
   0.7%
0
   0.0%
1
   0.7%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   1.6%
3
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
4
   0.7%
Other
3
   2.2%
2
   3.1%
9
   6.6%
0
   0.0%
1
   1.7%
3
   4.8%
18
   3.2%
Unknown
0
   0.0%
1
   1.6%
2
   1.5%
1
   1.0%
0
   0.0%
1
   1.6%
5
   0.9%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.6%
1
   0.2%
Not Reported
1
   0.7%
1
   1.6%
3
   2.2%
6
   5.8%
2
   3.3%
2
   3.2%
15
   2.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 137 participants 64 participants 136 participants 104 participants 60 participants 62 participants 563 participants
Canada 0 0 4 10 6 7 27
Austria 0 0 0 0 0 4 4
United States 132 52 115 83 20 11 413
Australia 5 12 17 11 23 18 86
France 0 0 0 0 0 6 6
Germany 0 0 0 0 0 2 2
Spain 0 0 0 0 11 14 25
1.Primary Outcome
Title Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
Hide Description The primary objective of this study is to characterize the percentage of patients with Grade 3 or higher diarrhea in patients with early-stage HER2 overexpressed/amplified (HER2+) breast cancer treated with neratinib when administered with intensive loperamide prophylaxis, after prior treatment with trastuzumab. Grade 3: Increase of >=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death.
Time Frame From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Hide Arm/Group Description:

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.

Neratinib

Loperamide

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.

Neratinib

Loperamide

Budesonide: 9 mg extended release tablets once daily with or without food for 28 days

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.

Neratinib

Loperamide

160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.

Neratinib

Loperamide

Overall Number of Participants Analyzed 137 64 136 104 60 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
30.7
(23.1 to 39.1)
28.1
(17.6 to 40.8)
20.6
(14.1 to 28.4)
32.7
(23.8 to 42.6)
13.3
(5.9 to 24.6)
27.4
(16.9 to 40.2)
2.Secondary Outcome
Title Percentage of Patients With Diarrhea by Grade, According to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), Version 4.0.
Hide Description Assess the percentage of patients with diarrhea after the administration of an anti-inflammatory agent, a bile acid sequestrant, or following two different dose-escalation regimens of neratinib, by maximum CTC grade. Grade 1: an increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline. Grade 2: Increase of 4 - 6 stools per day over baseline; moderate increase in ostomy output compared to baseline. Grade 3: Increase of >=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death.
Time Frame From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Hide Arm/Group Description:

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.

Neratinib

Loperamide

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.

Neratinib

Loperamide

Budesonide: 9 mg extended release tablets once daily with or without food for 28 days

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.

Neratinib

Loperamide

160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.

Neratinib

Loperamide

Overall Number of Participants Analyzed 137 64 136 104 60 62
Measure Type: Number
Unit of Measure: Percentage of participants
Percentage of Patients w Grade 1 Diarrhea 24.1 23.4 27.9 32.7 40.0 37.1
Percentage of Patients w Grade 2 Diarrhea 24.8 34.4 34.6 29.8 45.0 33.9
Percentage of Patients w Grade 3 Diarrhea 30.7 28.1 20.6 32.7 13.3 27.4
3.Secondary Outcome
Title Percentage of Patients With Serious Adverse Events and Other Adverse Events of Special Interest
Hide Description Assess the percentage of patients with serious adverse events (SAEs) and other adverse events of special interest (AESI). AESIs were selected based on the known safety profile of neratinib as well as typical key body system toxicity concerns generally reviewed for any new drug. These AESIs were grouped into the following categories: gastrointestinal toxicity (diarrhea and stomatitis), hepatotoxicity, pulmonary toxicity (interstitial lung disease), cardiac toxicity (LVEF decreased), and dermatologic toxicity (rash and nail disorders). The AESIs were analyzed by searching the clinical database for all TEAEs and SAEs using either Standardized MedDRA Queries (SMQs) or, if an applicable SMQ did not exist, a Sponsor-defined list of MedDRA preferred terms.
Time Frame From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least one dose of neratinib.
Arm/Group Title Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Hide Arm/Group Description:

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.

Neratinib

Loperamide

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.

Neratinib

Loperamide

Budesonide: 9 mg extended release tablets once daily with or without food for 28 days

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.

Neratinib

Loperamide

160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.

Neratinib

Loperamide

Overall Number of Participants Analyzed 137 64 136 104 60 62
Measure Type: Number
Unit of Measure: percentage of participants
Percentage of Patients with SAEs 6.57 6.25 6.62 2.88 8.33 8.06
Percentage of Patients with AESI-Gastrointestinal Toxicities (Diarrhoea and Stomatitis Broad Search) 81.75 87.5 83.82 96.15 98.33 98.39
Percentage of Patients with-Hepatotoxicities SMQ (Broad Search) 12.41 7.81 4.41 4.81 8.33 4.84
Percentage of Patients with AESI- Interstitial Lung Disease SMQ (Broad Search) 0 0 0 0 0 0
Percentage of Patients with AESI-Cardiac Toxicities SMQ (Broad Search) 5.84 6.25 10.29 7.69 10.00 4.84
Percentage of Patients with AESI - Dermatologic Toxicities (Rash and Nail Disorders) 12.41 37.50 23.53 18.27 11.67 30.65
Percentage of Patients with AESI-Gastrointestinal Toxicities (Narrow Search) 80.29 85.94 83.09 95.19 98.33 98.39
Percentage of Patients with AESI-Hepatotoxicities SMQ (Narrow Search) 10.95 7.81 3.68 3.85 8.33 4.84
Percentage of Patients with AESI- Interstitial Lung Disease SMQ (Narrow Search) 0 0 0 0 0 0
Percentage of Patients with AESI-Cardiac Toxicities SMQ (Narrow Search) 2.92 0 1.47 0.96 1.67 0
Time Frame From time of first dose, through 28 days after last dose, assessed up to 15.5 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Hide Arm/Group Description

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.

Neratinib

Loperamide

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.

Neratinib

Loperamide

Budesonide: 9 mg extended release tablets once daily with or without food for 28 days

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.

Neratinib

Loperamide

Colestipol: 2 g twice daily with or without food for one 28 day cycle

120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.

Neratinib

Loperamide

160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.

Neratinib

Loperamide

All-Cause Mortality
Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/137 (0.00%)   0/64 (0.00%)   0/136 (0.00%)   0/104 (0.00%)   0/60 (0.00%)   0/62 (0.00%) 
Hide Serious Adverse Events
Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/137 (6.57%)   4/64 (6.25%)   9/136 (6.62%)   3/104 (2.88%)   5/60 (8.33%)   5/62 (8.06%) 
Eye disorders             
Retinal detachment  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Gastrointestinal disorders             
Abdominal pain  1  0/137 (0.00%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Colitis  1  0/137 (0.00%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Diarrhoea  1  2/137 (1.46%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Nausea  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Pancreatitis  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  1/62 (1.61%) 
Stomatitis  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
General disorders             
Fat necrosis  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Pyrexia  1  0/137 (0.00%)  1/64 (1.56%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  1/62 (1.61%) 
Hepatobiliary disorders             
Cholecystitis  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  1/62 (1.61%) 
Cholecystitis acute  1  0/137 (0.00%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Cholelithiasis  1  0/137 (0.00%)  1/64 (1.56%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Infections and infestations             
Appendicitis  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  1/104 (0.96%)  0/60 (0.00%)  0/62 (0.00%) 
Bacteraemia  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Breast cellulitis  1  0/137 (0.00%)  1/64 (1.56%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Cellulitis  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  1/104 (0.96%)  0/60 (0.00%)  0/62 (0.00%) 
Device related infection  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  1/62 (1.61%) 
Gastroenteritis  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  1/104 (0.96%)  0/60 (0.00%)  0/62 (0.00%) 
Gastroenteritis viral  1  0/137 (0.00%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Influenza  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  1/62 (1.61%) 
Listeriosis  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  1/62 (1.61%) 
Lower respiratory tract infection  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Post procedural infection  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Sepsis  1  1/137 (0.73%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Upper respiratory tract infection  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Urinary tract infection  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Wound infection  1  0/137 (0.00%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Injury, poisoning and procedural complications             
Rib fracture  1  0/137 (0.00%)  1/64 (1.56%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Investigations             
Alanine aminotransferase increased  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Aspartate aminotransferase increased  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Electrocardiogram QT prolonged  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Dehydration  1  1/137 (0.73%)  0/64 (0.00%)  1/136 (0.74%)  1/104 (0.96%)  1/60 (1.67%)  0/62 (0.00%) 
Hypokalaemia  1  1/137 (0.73%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Malignant melanoma in situ  1  0/137 (0.00%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Nervous system disorders             
Seizure  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Syncope  1  0/137 (0.00%)  0/64 (0.00%)  2/136 (1.47%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Psychiatric disorders             
Confusional state  1  0/137 (0.00%)  0/64 (0.00%)  1/136 (0.74%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Pleural effusion  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Skin and subcutaneous tissue disorders             
Rash  1  0/137 (0.00%)  1/64 (1.56%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
Rash erythematous  1  1/137 (0.73%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  0/60 (0.00%)  0/62 (0.00%) 
1
Term from vocabulary, MedDRA (24.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Loperamide Budesonide and Loperamide Colestipol and Loperamide Colestipol With Loperamide as Needed Neratinib Dose Escalation 1 Neratinib Dose Escalation 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   137/137 (100.00%)   64/64 (100.00%)   136/136 (100.00%)   104/104 (100.00%)   60/60 (100.00%)   62/62 (100.00%) 
Blood and lymphatic system disorders             
Anaemia  1  8/137 (5.84%)  5/64 (7.81%)  1/136 (0.74%)  5/104 (4.81%)  0/60 (0.00%)  0/62 (0.00%) 
Ear and labyrinth disorders             
Vertigo  1  0/137 (0.00%)  4/64 (6.25%)  3/136 (2.21%)  0/104 (0.00%)  1/60 (1.67%)  0/62 (0.00%) 
Gastrointestinal disorders             
Abdominal discomfort  1  7/137 (5.11%)  2/64 (3.13%)  7/136 (5.15%)  5/104 (4.81%)  2/60 (3.33%)  0/62 (0.00%) 
Abdominal distension  1  21/137 (15.33%)  5/64 (7.81%)  22/136 (16.18%)  15/104 (14.42%)  6/60 (10.00%)  10/62 (16.13%) 
Abdominal pain  1  36/137 (26.28%)  12/64 (18.75%)  26/136 (19.12%)  27/104 (25.96%)  13/60 (21.67%)  15/62 (24.19%) 
Abdominal pain upper  1  5/137 (3.65%)  7/64 (10.94%)  16/136 (11.76%)  7/104 (6.73%)  3/60 (5.00%)  8/62 (12.90%) 
Constipation  1  78/137 (56.93%)  48/64 (75.00%)  93/136 (68.38%)  39/104 (37.50%)  22/60 (36.67%)  15/62 (24.19%) 
Diarrhoea  1  109/137 (79.56%)  55/64 (85.94%)  113/136 (83.09%)  99/104 (95.19%)  59/60 (98.33%)  61/62 (98.39%) 
Dry mouth  1  18/137 (13.14%)  6/64 (9.38%)  12/136 (8.82%)  5/104 (4.81%)  4/60 (6.67%)  3/62 (4.84%) 
Dyspepsia  1  12/137 (8.76%)  10/64 (15.63%)  16/136 (11.76%)  13/104 (12.50%)  7/60 (11.67%)  6/62 (9.68%) 
Flatulence  1  5/137 (3.65%)  6/64 (9.38%)  5/136 (3.68%)  2/104 (1.92%)  1/60 (1.67%)  3/62 (4.84%) 
Gastrooesophageal reflux disease  1  10/137 (7.30%)  5/64 (7.81%)  10/136 (7.35%)  6/104 (5.77%)  2/60 (3.33%)  4/62 (6.45%) 
Nausea  1  78/137 (56.93%)  32/64 (50.00%)  83/136 (61.03%)  64/104 (61.54%)  27/60 (45.00%)  28/62 (45.16%) 
Stomatitis  1  7/137 (5.11%)  4/64 (6.25%)  14/136 (10.29%)  13/104 (12.50%)  6/60 (10.00%)  6/62 (9.68%) 
Vomiting  1  36/137 (26.28%)  16/64 (25.00%)  43/136 (31.62%)  25/104 (24.04%)  9/60 (15.00%)  5/62 (8.06%) 
General disorders             
Asthenia  1  6/137 (4.38%)  1/64 (1.56%)  1/136 (0.74%)  4/104 (3.85%)  3/60 (5.00%)  2/62 (3.23%) 
Fatigue  1  73/137 (53.28%)  34/64 (53.13%)  65/136 (47.79%)  41/104 (39.42%)  28/60 (46.67%)  19/62 (30.65%) 
Pyrexia  1  6/137 (4.38%)  2/64 (3.13%)  10/136 (7.35%)  3/104 (2.88%)  2/60 (3.33%)  1/62 (1.61%) 
Infections and infestations             
Cellulitis  1  3/137 (2.19%)  1/64 (1.56%)  0/136 (0.00%)  2/104 (1.92%)  3/60 (5.00%)  0/62 (0.00%) 
Influenza  1  2/137 (1.46%)  0/64 (0.00%)  3/136 (2.21%)  4/104 (3.85%)  3/60 (5.00%)  0/62 (0.00%) 
Nasopharyngitis  1  5/137 (3.65%)  4/64 (6.25%)  2/136 (1.47%)  3/104 (2.88%)  1/60 (1.67%)  1/62 (1.61%) 
Upper respiratory tract infection  1  5/137 (3.65%)  7/64 (10.94%)  7/136 (5.15%)  5/104 (4.81%)  6/60 (10.00%)  2/62 (3.23%) 
Urinary tract infection  1  10/137 (7.30%)  2/64 (3.13%)  8/136 (5.88%)  9/104 (8.65%)  6/60 (10.00%)  5/62 (8.06%) 
Investigations             
Alanine aminotransferase increased  1  9/137 (6.57%)  4/64 (6.25%)  4/136 (2.94%)  3/104 (2.88%)  4/60 (6.67%)  2/62 (3.23%) 
Aspartate aminotransferase increased  1  4/137 (2.92%)  1/64 (1.56%)  3/136 (2.21%)  2/104 (1.92%)  3/60 (5.00%)  2/62 (3.23%) 
Blood glucose increased  1  0/137 (0.00%)  0/64 (0.00%)  0/136 (0.00%)  0/104 (0.00%)  3/60 (5.00%)  0/62 (0.00%) 
Weight decreased  1  10/137 (7.30%)  4/64 (6.25%)  11/136 (8.09%)  4/104 (3.85%)  1/60 (1.67%)  3/62 (4.84%) 
Metabolism and nutrition disorders             
Decreased appetite  1  26/137 (18.98%)  11/64 (17.19%)  24/136 (17.65%)  26/104 (25.00%)  8/60 (13.33%)  8/62 (12.90%) 
Dehydration  1  7/137 (5.11%)  6/64 (9.38%)  5/136 (3.68%)  4/104 (3.85%)  2/60 (3.33%)  2/62 (3.23%) 
Hypokalaemia  1  4/137 (2.92%)  1/64 (1.56%)  8/136 (5.88%)  2/104 (1.92%)  1/60 (1.67%)  0/62 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  10/137 (7.30%)  14/64 (21.88%)  15/136 (11.03%)  13/104 (12.50%)  9/60 (15.00%)  4/62 (6.45%) 
Back pain  1  10/137 (7.30%)  5/64 (7.81%)  9/136 (6.62%)  10/104 (9.62%)  4/60 (6.67%)  2/62 (3.23%) 
Muscle spasms  1  15/137 (10.95%)  8/64 (12.50%)  14/136 (10.29%)  15/104 (14.42%)  12/60 (20.00%)  8/62 (12.90%) 
Myalgia  1  3/137 (2.19%)  4/64 (6.25%)  6/136 (4.41%)  5/104 (4.81%)  2/60 (3.33%)  3/62 (4.84%) 
Pain in extremity  1  7/137 (5.11%)  3/64 (4.69%)  7/136 (5.15%)  5/104 (4.81%)  2/60 (3.33%)  3/62 (4.84%) 
Nervous system disorders             
Dizziness  1  19/137 (13.87%)  6/64 (9.38%)  21/136 (15.44%)  20/104 (19.23%)  9/60 (15.00%)  8/62 (12.90%) 
Headache  1  26/137 (18.98%)  12/64 (18.75%)  20/136 (14.71%)  24/104 (23.08%)  13/60 (21.67%)  8/62 (12.90%) 
Neuropathy peripheral  1  4/137 (2.92%)  3/64 (4.69%)  3/136 (2.21%)  6/104 (5.77%)  0/60 (0.00%)  1/62 (1.61%) 
Paraesthesia  1  3/137 (2.19%)  1/64 (1.56%)  3/136 (2.21%)  0/104 (0.00%)  5/60 (8.33%)  0/62 (0.00%) 
Psychiatric disorders             
Anxiety  1  5/137 (3.65%)  4/64 (6.25%)  3/136 (2.21%)  3/104 (2.88%)  3/60 (5.00%)  2/62 (3.23%) 
Insomnia  1  6/137 (4.38%)  8/64 (12.50%)  10/136 (7.35%)  8/104 (7.69%)  3/60 (5.00%)  4/62 (6.45%) 
Reproductive system and breast disorders             
Breast pain  1  4/137 (2.92%)  7/64 (10.94%)  8/136 (5.88%)  6/104 (5.77%)  1/60 (1.67%)  0/62 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  7/137 (5.11%)  7/64 (10.94%)  9/136 (6.62%)  8/104 (7.69%)  1/60 (1.67%)  0/62 (0.00%) 
Dyspnoea  1  9/137 (6.57%)  4/64 (6.25%)  4/136 (2.94%)  4/104 (3.85%)  3/60 (5.00%)  1/62 (1.61%) 
Epistaxis  1  2/137 (1.46%)  2/64 (3.13%)  9/136 (6.62%)  4/104 (3.85%)  3/60 (5.00%)  4/62 (6.45%) 
Skin and subcutaneous tissue disorders             
Dermatitis acneiform  1  2/137 (1.46%)  4/64 (6.25%)  5/136 (3.68%)  1/104 (0.96%)  1/60 (1.67%)  4/62 (6.45%) 
Dry skin  1  6/137 (4.38%)  8/64 (12.50%)  7/136 (5.15%)  10/104 (9.62%)  4/60 (6.67%)  9/62 (14.52%) 
Onychoclasis  1  5/137 (3.65%)  3/64 (4.69%)  6/136 (4.41%)  4/104 (3.85%)  3/60 (5.00%)  6/62 (9.68%) 
Rash  1  7/137 (5.11%)  12/64 (18.75%)  15/136 (11.03%)  10/104 (9.62%)  1/60 (1.67%)  8/62 (12.90%) 
Vascular disorders             
Hot flush  1  8/137 (5.84%)  6/64 (9.38%)  17/136 (12.50%)  7/104 (6.73%)  7/60 (11.67%)  4/62 (6.45%) 
1
Term from vocabulary, MedDRA (24.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Director, Clinical Operations
Organization: Puma Biotechnology, Inc.
Phone: 1-424-248-6500
EMail: clinicaltrials@pumabiotechnology.com
Layout table for additonal information
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT02400476    
Other Study ID Numbers: PUMA-NER-6201
2015-004374-15 ( EudraCT Number )
First Submitted: February 17, 2015
First Posted: March 27, 2015
Results First Submitted: February 28, 2022
Results First Posted: May 6, 2022
Last Update Posted: May 6, 2022