Trial Outcomes & Findings for Phase I Open Label Trial to Assess Safety of BIBW 2992 (Afatinib) in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer. (NCT NCT00950742)

NCT ID: NCT00950742

Last Updated: 2025-02-10

Results Overview

Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Important Limitations and Caveats are provided in the respective section.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 18 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2025-02-10

Participant Flow

This was an open-label dose escalation study using a standard 3+3 dose escalation design, dose cohorts are presented here.

Participant milestones

Measure	Afatinib 20mg + Herceptin Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.	Afatinib 30mg + Herceptin Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.
Overall Study STARTED	16	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	16	2

Reasons for withdrawal

Measure	Afatinib 20mg + Herceptin Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.	Afatinib 30mg + Herceptin Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.
Overall Study Other Adverse Event	1	0
Overall Study Withdrawal by Subject	3	0
Overall Study Progressive Disease	6	2
Overall Study Dose limiting toxicity	6	0

Baseline Characteristics

Phase I Open Label Trial to Assess Safety of BIBW 2992 (Afatinib) in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

Baseline characteristics by cohort

Measure	Afatinib 20mg + Herceptin n=16 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.	Afatinib 30mg + Herceptin n=2 Participants Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.	Total n=18 Participants Total of all reporting groups
Age, Continuous	62.3 years STANDARD_DEVIATION 10.6 • n=5 Participants	52.5 years STANDARD_DEVIATION 6.4 • n=7 Participants	61.2 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	2 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Treated set (TS). TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. 3 patients were excluded as they were not evaluable for determination of maximum tolerated dose.

Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Important Limitations and Caveats are provided in the respective section.

Outcome measures

Measure	Afatinib 20mg + Herceptin n=13 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin n=2 Participants Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Number of Participants With Dose Limiting Toxicities (DLT)	4 Participants	2 Participants

PRIMARY outcome

Timeframe: 28 days

Population: TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. 3 patients were excluded as they were not evaluable for determination of maximum tolerated dose.

The MTD was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. It was determined using a standard 3 + 3 dose escalation cohort design. To confirm the MTD, the MTD cohort was to be expanded to 18 patients with no more than 3/18 patients experiencing a DLT. Please refer to CAVEATs and Limitations.

Outcome measures

Measure	Afatinib 20mg + Herceptin n=8 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R)	20 mg	—

SECONDARY outcome

Timeframe: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.

Population: TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.

Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).

Outcome measures

Measure	Afatinib 20mg + Herceptin n=16 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin n=2 Participants Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Number of Patients With Objective Response (OR)	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.

Population: TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.

Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or not evaluable.

Outcome measures

Measure	Afatinib 20mg + Herceptin n=16 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin n=2 Participants Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Number of Patients With Best Overall Response Stable Disease	4 Participants	1 Participants
Number of Patients With Best Overall Response Progressive Disease	0 Participants	1 Participants
Number of Patients With Best Overall Response Complete Response	0 Participants	0 Participants
Number of Patients With Best Overall Response Partial Response	2 Participants	0 Participants
Number of Patients With Best Overall Response Not evaluable	10 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline until disease progression, death or data cut-off.

Population: TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.

PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the response evaluation criteria in solid tumors (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.

Outcome measures

Measure	Afatinib 20mg + Herceptin n=16 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin n=2 Participants Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Progression Free Survival (PFS)	113.0 Days Interval 101.0 to 388.0	83.5 Days Interval 56.0 to 111.0

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing

Population: Patients with no data available for the relevant parameter and dose were excluded from analysis.

Pre-dose Concentrations of Afatinib in Plasma at Steady State on Days 8, 15 and 29 (Cpre,ss,8, Cpre,ss,15 and Cpre,ss,29) and Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss).

Outcome measures

Measure	Afatinib 20mg + Herceptin n=16 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Summary of Concentration of Afatinib in Plasma Cpre,ss,29 (N=8)	9.15 ng/mL Geometric Coefficient of Variation 64.7	—
Summary of Concentration of Afatinib in Plasma Cpre,ss,8 (N=11)	9.75 ng/mL Geometric Coefficient of Variation 69.5	—
Summary of Concentration of Afatinib in Plasma Cpre,ss,15 (N=13)	9.94 ng/mL Geometric Coefficient of Variation 72.4	—
Summary of Concentration of Afatinib in Plasma Cmax,ss (N=10)	17.9 ng/mL Geometric Coefficient of Variation 80.9	—

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing

Population: Patients with no data available for the relevant parameter and dose were excluded from analysis.

tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state

Outcome measures

Measure	Afatinib 20mg + Herceptin n=11 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)	4.25 hours Interval 0.75 to 7.02	—

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing

Population: Patients with no data available for the relevant parameter and dose were excluded from analysis.

Pre-dose Concentrations of Herceptin in Plasma on Days 8, 15 and 29 (Cpre,8, Cpre,15 and Cpre,29) and Maximum Concentration of Herceptin in Plasma on Days 1, 15 and 29 (Cmax,1, Cmax,15 and Cmax,29).

Outcome measures

Measure	Afatinib 20mg + Herceptin n=16 Participants Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.	Afatinib 30mg + Herceptin Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.
Summary of Concentration of Herceptin in Plasma Cpre,8 (N=14)	43600 ng/mL Geometric Coefficient of Variation 53.9	—
Summary of Concentration of Herceptin in Plasma Cpre,15 (N=13)	47200 ng/mL Geometric Coefficient of Variation 47.0	—
Summary of Concentration of Herceptin in Plasma Cpre,29 (N=11)	46200 ng/mL Geometric Coefficient of Variation 30.9	—
Summary of Concentration of Herceptin in Plasma Cmax,1 (N=14)	122000 ng/mL Geometric Coefficient of Variation 27.9	—
Summary of Concentration of Herceptin in Plasma Cmax,15 (N=12)	93000 ng/mL Geometric Coefficient of Variation 24.9	—
Summary of Concentration of Herceptin in Plasma Cmax,29 (N=7)	93200 ng/mL Geometric Coefficient of Variation 16.9	—

Adverse Events

Afatinib 20mg + Herceptin

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Afatinib 30mg + Herceptin

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Afatinib 20mg + Herceptin n=16 participants at risk Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression.	Afatinib 30mg + Herceptin n=2 participants at risk Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression.
Gastrointestinal disorders Diarrhoea	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Renal and urinary disorders Renal failure acute	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)

Other adverse events

Measure	Afatinib 20mg + Herceptin n=16 participants at risk Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression.	Afatinib 30mg + Herceptin n=2 participants at risk Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression.
Blood and lymphatic system disorders Anaemia	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Ear and labyrinth disorders Vertigo	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Eye disorders Conjunctivitis	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Eye disorders Dry eye	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Eye disorders Eye pain	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Eye disorders Foreign body sensation in eyes	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Eye disorders Lacrimation increased	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Eye disorders Ocular hyperaemia	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Eye disorders Vision blurred	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Abdominal discomfort	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Abdominal pain	18.8% 3/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Abdominal pain upper	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Chapped lips	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Cheilitis	18.8% 3/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Constipation	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Diarrhoea	87.5% 14/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	100.0% 2/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Dry mouth	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Dyspepsia	31.2% 5/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Gastrooesophageal reflux disease	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Gingival bleeding	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Lip dry	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Lip swelling	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Mouth ulceration	31.2% 5/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Nausea	62.5% 10/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Oedema mouth	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Oral mucosal erythema	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Oral pain	37.5% 6/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Stomatitis	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Tongue ulceration	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Gastrointestinal disorders Vomiting	31.2% 5/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Axillary pain	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Catheter site swelling	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Crepitations	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Fatigue	56.2% 9/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Influenza like illness	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Local swelling	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Mucosal inflammation	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Pain	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Pyrexia	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Secretion discharge	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Spinal pain	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
General disorders Tenderness	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Cellulitis	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Device related infection	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Fungal infection	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Fungal skin infection	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Hordeolum	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Influenza	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Localised infection	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Lower respiratory tract infection	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Nail bed infection	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Nasopharyngitis	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Oral candidiasis	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Post procedural infection	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Purulent discharge	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Sinusitis	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Tinea pedis	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Infections and infestations Upper respiratory tract infection	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Injury, poisoning and procedural complications Arthropod sting	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Injury, poisoning and procedural complications Muscle strain	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Alanine aminotransferase increased	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Aspartate aminotransferase increased	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Blood alkaline phosphatase increased	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Blood bilirubin increased	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Blood creatine phosphokinase increased	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Ejection fraction decreased	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Haemoglobin decreased	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations International normalised ratio increased	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Transaminases increased	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Investigations Weight decreased	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Metabolism and nutrition disorders Decreased appetite	56.2% 9/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Metabolism and nutrition disorders Dehydration	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Metabolism and nutrition disorders Hypokalaemia	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Musculoskeletal and connective tissue disorders Axillary mass	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Musculoskeletal and connective tissue disorders Limb discomfort	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Musculoskeletal and connective tissue disorders Muscle spasms	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Musculoskeletal and connective tissue disorders Myalgia	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Musculoskeletal and connective tissue disorders Pain in extremity	18.8% 3/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Nervous system disorders Ageusia	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Nervous system disorders Brain oedema	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Nervous system disorders Dizziness	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Nervous system disorders Dysgeusia	18.8% 3/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Nervous system disorders Headache	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Nervous system disorders Neuropathy peripheral	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Nervous system disorders Paraesthesia	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Psychiatric disorders Depressed mood	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Psychiatric disorders Depression	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Renal and urinary disorders Chromaturia	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Renal and urinary disorders Renal impairment	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Reproductive system and breast disorders Breast discharge	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Reproductive system and breast disorders Breast disorder	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Reproductive system and breast disorders Breast pain	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Reproductive system and breast disorders Vulvovaginal dryness	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Cough	18.8% 3/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Dry throat	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Epistaxis	31.2% 5/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Lung disorder	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Nasal discomfort	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Nasal dryness	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Nasal ulcer	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Rhinalgia	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	100.0% 2/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Acne	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Dermatitis acneiform	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Dermatitis allergic	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Dry skin	37.5% 6/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	100.0% 2/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Erythema	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Ingrowing nail	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Nail disorder	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Onychalgia	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Onychoclasis	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	12.5% 2/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Pruritus	18.8% 3/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Rash	56.2% 9/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	100.0% 2/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Scab	0.00% 0/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	50.0% 1/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Skin and subcutaneous tissue disorders Skin fissures	37.5% 6/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	100.0% 2/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Vascular disorders Haemorrhage	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)
Vascular disorders Hypertension	6.2% 1/16 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)	0.00% 0/2 • First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days)

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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