Trial Outcomes & Findings for Phase I Trial of Afatinib and Trastuzumab in HER2 Overexpressing Cancer. (NCT NCT01649271)
NCT ID: NCT01649271
Last Updated: 2025-02-11
Results Overview
Maximum Tolerated Dose (MTD) of Afatinib in combination with trastuzumab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD was defined as the highest dose studied at which the incidence of a DLT was less than 17% (i.e. 1/6 patients) during the first cycle. One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
First 21 days treatment cycle
Results posted on
2025-02-11
Participant Flow
HER2: Human Epidermal Growth Factor Receptor 2; RECIST,v1.1: Response Evaluation Criteria In Solid Tumors, version 1.1
Phase Ia: Open label, uncontrolled, dose escalation study of afatinib given continuously in combination with trastuzumab administered every 3 weeks. Phase Ib: Open label, uncontrolled study to explore the efficacy, safety, pharmacokinetics \& biomarkers of afatinib at the MTD dosage, with 3- weekly trastuzumab.
Participant milestones
| Measure |
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg
In each 21 day treatment cycle, patients were administered orally 20 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
7
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
7
|
Reasons for withdrawal
| Measure |
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg
In each 21 day treatment cycle, patients were administered orally 20 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Overall Study
Progressive disease
|
4
|
5
|
|
Overall Study
Other Adverse Event
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Other than stated above
|
1
|
0
|
Baseline Characteristics
Phase I Trial of Afatinib and Trastuzumab in HER2 Overexpressing Cancer.
Baseline characteristics by cohort
| Measure |
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg
n=6 Participants
In each 21 day treatment cycle, patients were administered orally 20 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
n=7 Participants
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.8 Years
STANDARD_DEVIATION 3.7 • n=5 Participants
|
48.4 Years
STANDARD_DEVIATION 7.6 • n=7 Participants
|
54.2 Years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First 21 days treatment cyclePopulation: Treated set: This analysis set includes all patients who were documented to have taken at least one dose of study medication.
Maximum Tolerated Dose (MTD) of Afatinib in combination with trastuzumab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD was defined as the highest dose studied at which the incidence of a DLT was less than 17% (i.e. 1/6 patients) during the first cycle. One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.
Outcome measures
| Measure |
Phase Ia: Afatinib +Trastuzumab 8 mg/kg
n=12 Participants
In each 21 day treatment cycle, patients were administered orally afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
MTD of Afatinib in Combination With Trastuzumab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib).
|
20 mg
|
—
|
PRIMARY outcome
Timeframe: First 21-day treatment cyclePopulation: Treated set
Number of Patients With Dose Limiting Toxicity (DLT) occurring during Cycle 1 based on the investigator assessment. One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.
Outcome measures
| Measure |
Phase Ia: Afatinib +Trastuzumab 8 mg/kg
n=6 Participants
In each 21 day treatment cycle, patients were administered orally afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
n=6 Participants
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Dose Limiting Toxicities During cycle1
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until End of Treatment (EOT); up to 33 monthsPopulation: Treated set Missing: First image time point not reached before discontinuation.
BOR represents the best response a patient had during their time in study from start of treatment until progression, the last evaluable assessment in absence of progression or start of subsequent anticancer therapy. For patients that died, BOR was to be calculated based on data up to last evaluable RECIST,v1.1 assessment prior to death. Death did not contribute as PD for BOR. As per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD. PD: At least a 20% increase in SLD of TL taking as reference the smallest SLD recorded since treatment started, together with an absolute increase in SLD of at least 5mm. SD: Neither sufficient shrinkage to qualify for PR, taking as reference the baseline SLD, nor sufficient increase to qualify for PD.
Outcome measures
| Measure |
Phase Ia: Afatinib +Trastuzumab 8 mg/kg
n=6 Participants
In each 21 day treatment cycle, patients were administered orally afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
n=7 Participants
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Best Overall Response (BOR)
Complete Response (CR)
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Best Overall Response (BOR)
Partial Response (PR)
|
16.7 percentage of participants
|
0.0 percentage of participants
|
|
Best Overall Response (BOR)
Stable Disease (SD)
|
16.7 percentage of participants
|
100.0 percentage of participants
|
|
Best Overall Response (BOR)
Progressive Disease (PD)
|
50.0 percentage of participants
|
0.0 percentage of participants
|
|
Best Overall Response (BOR)
Missing
|
16.7 percentage of participants
|
0.0 percentage of participants
|
|
Best Overall Response (BOR)
Not Evaluable
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 33 monthsPopulation: Treated set
Objective Response (OR) was defined as best overall response of complete response (CR) or partial response (PR), where best overall response was determined according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 from first administration of study medication until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. As Per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD.
Outcome measures
| Measure |
Phase Ia: Afatinib +Trastuzumab 8 mg/kg
n=6 Participants
In each 21 day treatment cycle, patients were administered orally afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
n=7 Participants
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Objective Response
|
16.7 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 33 monthsPopulation: Treated set
Clinical benefit was defined as best overall response of CR or PR or stable disease (SD) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. As Per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD. SD: Neither sufficient shrinkage to qualify for PR, taking as reference the baseline SLD, nor sufficient increase to qualify for PD.
Outcome measures
| Measure |
Phase Ia: Afatinib +Trastuzumab 8 mg/kg
n=6 Participants
In each 21 day treatment cycle, patients were administered orally afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
n=7 Participants
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Clinical Benefit
|
33.3 percentage of participants
|
100.0 percentage of participants
|
Adverse Events
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg
Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
Serious events: 4 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg
n=6 participants at risk
In each 21 day treatment cycle, patients were administered orally 20 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
n=7 participants at risk
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
Chest pain
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
General physical health deterioration
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Hepatobiliary disorders
Biliary colic
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Vascular disorders
Jugular vein thrombosis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
Other adverse events
| Measure |
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg
n=6 participants at risk
In each 21 day treatment cycle, patients were administered orally 20 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg
n=7 participants at risk
In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Cardiac disorders
Cardiotoxicity
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Eye disorders
Dry eye
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Eye disorders
Lacrimation increased
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
28.6%
2/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
6/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
85.7%
6/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Duodenal ulcer
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Mouth ulceration
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Nausea
|
33.3%
2/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Perianal erythema
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
42.9%
3/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Tongue oedema
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
Asthenia
|
66.7%
4/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
71.4%
5/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
Face oedema
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
Fatigue
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
Influenza like illness
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
Pyrexia
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
General disorders
Xerosis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Hepatobiliary disorders
Hepatocellular injury
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Bronchitis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
28.6%
2/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Conjunctivitis
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Cystitis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Folliculitis
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Herpes virus infection
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Herpes zoster
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Oral herpes
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Paronychia
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
71.4%
5/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Rash pustular
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Investigations
Alanine aminotransferase increased
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Investigations
Blood creatinine increased
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
28.6%
2/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Investigations
Glomerular filtration rate decreased
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Investigations
Weight decreased
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
28.6%
2/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
42.9%
3/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
28.6%
2/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
50.0%
3/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pyogenic granuloma
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Nervous system disorders
Paraesthesia
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Psychiatric disorders
Depression
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
33.3%
2/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal mucosal disorder
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Acne
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Onycholysis
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
0.00%
0/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
2/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
71.4%
5/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
16.7%
1/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
|
Skin and subcutaneous tissue disorders
Skin reaction
|
0.00%
0/6 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
14.3%
1/7 • From first dose administration of the study medication to 28 days after last drug administration; up to 33 months
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER