Influence of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Various Doses of Afatinib

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01298063
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arms: 3

Study Details

Study Description

Brief Summary

Up to 38 subjects entered with the aim of entering 8 subjects with mild liver impairment (at highest dose of afatinib), 8 subjects with moderate liver impairment (at either highest dose or two lower doses) and 8 healthy matched controls to each of this two groups.

Condition or Disease	Intervention/Treatment	Phase
Liver Diseases; Healthy	Drug: Afatinib; Drug: Afatinib; Drug: Afatinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetics, Safety and Tolerability of Different Oral Doses of Afatinib, in Subjects With Mild to Moderate Hepatic Impairment Compared to Healthy Subjects - a Phase I, Single-dose, Open-label, Dose-escalation Study in a Matched Group Design
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Afatinib Group A, B (2), D healthy subjects, mild and moderate liver impaired subjects to receive one single dose treatment containing the highest dose afatinib	Drug: Afatinib; 1 tablet, once qd in the morning
Experimental: Afatinib Group B (3), D healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the medium dose of afatinib	Drug: Afatinib; 1 tablet, once qd in the morning
Experimental: Afatinib Group B (1), D healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the low dose of afatinib	Drug: Afatinib; 1 tablet, once qd in the morning

Outcome Measures

Primary Outcome Measures

1. Area Under Curve From 0 to Infinity (AUC0-infinity) [30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing]

   AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

2. Maximum Concentration (Cmax) [30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing]

   Cmax represents the maximum measured concentration of the analyte in plasma

Secondary Outcome Measures

1. Area Under Curve From 0 to tz (AUC0-tz) [30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing]

   AUC0-tz represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point

2. Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability [First administration of trial medication until 28 days after last administration of trial medication]

   Clinical relevant abnormalitites for physical examination, vital signs, 12-lead electrocardiogramm (ECG), clinical laboratory test (including hematology, clinical chemistry, coagulation, urinalysis), adverse event, investigator's global tolerability. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

Healthy subjects:

1. Healthy males and females according to a complete medical history, including a physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead Electrocardiogram, and clinical laboratory tests. The healthy subjects must meet the matching criteria based on the matching approach (cf. Section 3.3).

2. Age =18 and =75 years

3. Body Mass Index =18.5 and =34 kg/m2

4. Creatinine clearance >70 mL/min according to Cockroft & Gault (for healthy volunteers, cf. Section 10.2)

5. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation. Hepatically impaired subjects as determined by a hepatologist/ gastroenterologist:

6. Male and female liver impaired subjects determined by results of screening classified as Child-Pugh A; Child-Pugh score of 5-6 points or as Child-Pugh B; Child-Pugh score of 7-9 points, cf. Section 10.2. Child-Pugh criteria must be stable for at least 3 months prior to screening and during the trial.

7. Age =18 and =75 years

8. Body Mass Index =18.5 and =34 kg/m2

9. Creatinine clearance >40 mL/min according to Cockroft & Gault (for liver impaired subjects, cf. Section 10.2)

10. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.

For all females:

1. Postmenopausal female subjects (postmenopausal defined as at least 1 year of spontaneous amenorrhea [in questionable cases or spontaneous amenorrhea below 1 year a blood sample with simultaneous follicle stimulating hormone (FSH) above 40 IU/l and estradiol below 30 ng/l is confirmatory]) or adequate contraception* for female subjects of childbearing potential during the study and until 2 months after study completion, e.g. any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to first study drug administration, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile have to use an additional barrier method (e.g. condom).

Exclusion criteria:

Any relevant deviation from healthy conditions (excluded conditions caused by liver impairment)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1200.86.1 Boehringer Ingelheim Investigational Site	Kiel		Germany

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01298063
• Other Study ID Numbers: 1200.86; 2010-021140-18
• First Posted: Feb 17, 2011
• Last Update Posted: Dec 31, 2013
• Last Verified: Aug 1, 2013

• Additional relevant MeSH terms: Liver Diseases; Afatinib

Study Results

Participant Flow

Arm/Group Title	50 mg Afatinib Group A	30 mg Afatinib Group B1	50 mg Afatinib Group B2	50 mg Afatinib Group C	50 mg Afatinib Group D
Arm/Group Description	Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 milligram (mg) Afatinib (One tablet qd in the morning).	Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Period Title: Overall Study
STARTED	8	3	8	8	8
COMPLETED	8	3	8	8	8
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	50 mg Afatinib Group A	30 mg Afatinib Group B1	50 mg Afatinib Group B2	50 mg Afatinib Group C	50 mg Afatinib Group D	Total
Arm/Group Description	Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).	Total of all reporting groups
Overall Participants	8	3	8	8	8	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.9 (9.0)	64.3 (6.1)	54.8 (9.0)	55.9 (12.6)	53.1 (7.9)	55.3 (9.5)
Sex: Female, Male (Count of Participants)
Female	2 25%	0 0%	3 37.5%	2 25%	3 37.5%	10 28.6%
Male	6 75%	3 100%	5 62.5%	6 75%	5 62.5%	25 71.4%

Outcome Measures

1. Primary Outcome

Title	Area Under Curve From 0 to Infinity (AUC0-infinity)
Description	AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity
Time Frame	30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set includes all evaluable matched subjects in the treated set providing at least 1 observation for at least 1 PK endpoint without important protocol violations. Group B1 was not included in the primary analysis set for comparison.

Arm/Group Title	50 mg Afatinib Group A	30 mg Afatinib Group B1	50 mg Afatinib Group B2	50 mg Afatinib Group C	50 mg Afatinib Group D
Arm/Group Description	Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 milligram (mg) Afatinib (One tablet qd in the morning).	Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Measure Participants	8	3	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	886 (53.7)	552 (42.1)	934 (31.0)	956 (22.7)	985 (32.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50 mg Afatinib Group A, 50 mg Afatinib Group C
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Relative bioavailability
Statistical Test of Hypothesis	p-Value	0.1998
	Comments	P-value for ratio outside interval 80 - 125 percent
	Method	ANOVA
	Comments	Adjusted (by treatment) geometric mean ratio
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	92.64
	Confidence Interval	(2-Sided) 90%; 67.960 to 126.270
	Parameter Dispersion	Type: Standard Deviation; Value: 33.6
	Estimation Comments	The standard deviation is actually the intra individual geometric coefficient of variation

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	50 mg Afatinib Group B2, 50 mg Afatinib Group D
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Relative bioavailability
Statistical Test of Hypothesis	p-Value	0.1440
	Comments	P-value for ratio outside interval 80 - 125 percent
	Method	ANOVA
	Comments	Adjusted (by treatment) geometric mean ratio
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	94.88
	Confidence Interval	(2-Sided) 90%; 72.278 to 124.549
	Parameter Dispersion	Type: Standard Deviation; Value: 31.6
	Estimation Comments	The standard deviation is actually the intra individual geometric coefficient of variation

2. Primary Outcome

Title	Maximum Concentration (Cmax)
Description	Cmax represents the maximum measured concentration of the analyte in plasma
Time Frame	30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing

Outcome Measure Data

Analysis Population Description

PK analysis set. Group B1 was not included in the primary analysis set for comparison.

Arm/Group Title	50 mg Afatinib Group A	30 mg Afatinib Group B1	50 mg Afatinib Group B2	50 mg Afatinib Group C	50 mg Afatinib Group D
Arm/Group Description	Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Measure Participants	8	3	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	33.7 (51.7)	17.5 (44.1)	39.5 (40.1)	30.7 (33.7)	31.1 (46.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50 mg Afatinib Group A, 50 mg Afatinib Group C
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Relative bioavailability
Statistical Test of Hypothesis	p-Value	0.2002
	Comments	P-value for ratio outside interval 80 - 125 percent
	Method	ANOVA
	Comments	Adjusted (by treatment) geometric mean ratio
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	109.47
	Confidence Interval	(2-Sided) 90%; 82.683 to 144.947
	Parameter Dispersion	Type: Standard Deviation; Value: 30.3
	Estimation Comments	The standard deviation is actually the intra individual geometric coefficient of variation

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	50 mg Afatinib Group B2, 50 mg Afatinib Group D
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Relative bioavailability
Statistical Test of Hypothesis	p-Value	0.5281
	Comments	P-value for ratio outside interval 80 - 125 percent
	Method	ANOVA
	Comments	Adjusted (by treatment) geometric mean ratio
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	126.89
	Confidence Interval	(2-Sided) 90%; 86.028 to 187.159
	Parameter Dispersion	Type: Standard Deviation; Value: 42.8
	Estimation Comments	The standard deviation is actually the intra individual geometric coefficient of variation

3. Secondary Outcome

Title	Area Under Curve From 0 to tz (AUC0-tz)
Description	AUC0-tz represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point
Time Frame	30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing

Outcome Measure Data

Analysis Population Description

PK analysis set. Group B1 was not included in the primary analysis set for comparison.

Arm/Group Title	50 mg Afatinib Group A	30 mg Afatinib Group B1	50 mg Afatinib Group B2	50 mg Afatinib Group C	50 mg Afatinib Group D
Arm/Group Description	Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Measure Participants	8	3	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	842 (50.8)	519 (39.1)	904 (31.4)	930 (22.5)	956 (33.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50 mg Afatinib Group A, 50 mg Afatinib Group C
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Relative bioavailability
Statistical Test of Hypothesis	p-Value	0.2309
	Comments	P-value for ratio outside interval 80 - 125 percent
	Method	ANOVA
	Comments	Adjusted (by treatment) geometric mean ratio
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	90.61
	Confidence Interval	(2-Sided) 90%; 66.915 to 122.705
	Parameter Dispersion	Type: Standard Deviation; Value: 32.8
	Estimation Comments	The standard deviation is actually the intra individual geometric coefficient of variation

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	50 mg Afatinib Group B2, 50 mg Afatinib Group D
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Relative bioavailability
Statistical Test of Hypothesis	p-Value	0.1546
	Comments	P-value for ratio outside interval 80 - 125 percent
	Method	ANOVA
	Comments	Adjusted (by treatment) geometric mean ratio
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	94.49
	Confidence Interval	(2-Sided) 90%; 71.563 to 124.764
	Parameter Dispersion	Type: Standard Deviation; Value: 32.4
	Estimation Comments	The standard deviation is actually the intra individual geometric coefficient of variation

4. Secondary Outcome

Title	Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability
Description	Clinical relevant abnormalitites for physical examination, vital signs, 12-lead electrocardiogramm (ECG), clinical laboratory test (including hematology, clinical chemistry, coagulation, urinalysis), adverse event, investigator's global tolerability. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Time Frame	First administration of trial medication until 28 days after last administration of trial medication

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	50 mg Afatinib Group A	30 mg Afatinib Group B1	50 mg Afatinib Group B2	50 mg Afatinib Group C	50 mg Afatinib Group D
Arm/Group Description	Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Measure Participants	8	3	8	8	8
Lipase increased	1 12.5%	0 0%	0 0%	0 0%	0 0%
Hyperlipasaemia	0 0%	1 33.3%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	First administration of trial medication until 28 days after last administration of trial medication
Arm/Group Title	50 mg Afatinib Group A		30 mg Afatinib Group B1		50 mg Afatinib Group B2		50 mg Afatinib Group C		50 mg Afatinib Group D
Arm/Group Description	Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning).		Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).		Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).		Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).		Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
All Cause Mortality
	50 mg Afatinib Group A		30 mg Afatinib Group B1		50 mg Afatinib Group B2		50 mg Afatinib Group C		50 mg Afatinib Group D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	50 mg Afatinib Group A		30 mg Afatinib Group B1		50 mg Afatinib Group B2		50 mg Afatinib Group C		50 mg Afatinib Group D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/3 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	50 mg Afatinib Group A		30 mg Afatinib Group B1		50 mg Afatinib Group B2		50 mg Afatinib Group C		50 mg Afatinib Group D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)		1/3 (33.3%)		1/8 (12.5%)		1/8 (12.5%)		0/8 (0%)
Gastrointestinal disorders
Diarrhoea	1/8 (12.5%)		0/3 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Dyspepsia	0/8 (0%)		0/3 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Nausea	1/8 (12.5%)		0/3 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Investigations
Lipase increased	1/8 (12.5%)		0/3 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Metabolism and nutrition disorders
Hyperlipasaemia	0/8 (0%)		1/3 (33.3%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Nervous system disorders
Headache	1/8 (12.5%)		0/3 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Vascular disorders
Phlebitis	0/8 (0%)		0/3 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.