GIOTRIF in First Line Therapy of Advanced NSCLC With EGFR-mutations

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02047903
• Collaborator: (none)
• Enrollment: 161
• Location: 1
• Actual Duration (Months): 57.9
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

This observational study will investigate the efficacy, safety, tolerability and symptom control of GIOTRIF (Afatinib) in daily routine first-line therapy in patients with locally advanced or metastatic NSCLC harboring EGFR-mutations. Eligible NSCLC patients, for whom the treating physician has decided to initiate treatment with GIOTRIF in first line according to the local label, will be followed up for approximately 24 months.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Afatinib

Detailed Description

Study Design:

Study Design

• Study Type: Observational
• Actual Enrollment: 161 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: An Observational Study of GIOTRIF (Afatinib) for First Line Therapy in Patients With Advanced Non Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR)-Mutations.
• Actual Study Start Date: Mar 5, 2014
• Actual Primary Completion Date: Dec 31, 2018
• Actual Study Completion Date: Dec 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Afatinib	Drug: Afatinib; 50, 40, 30 or 20 mg

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Rate After 12 Months [After 12 months]

   The rate (probability) of being progression free after 12 months. PFS is defined as the time from first administration of the trial drug until objective tumor progression or death. The rate is the Kaplan-Meier estimated percent probability.

Secondary Outcome Measures

1. Objective Response Rate (ORR) [From the initial dose of study drug until end of the treatment period, up to 48 months.]

   Objective response rate is calculated as a percentage of participants with complete response (CR) or partial response (PR) (i.e CR+PR) as best unconfirmed response. Here CR and PR were determined by investigators by using RECIST/WHO/clinical evidence as investigators deemed appropriate.

2. Disease Control Rate (DCR) [From the initial dose of study drug until end of the treatment period, up to 48 months.]

   Percentage of participants with controlled disease (CR + PR + stable disease (SD)) as best unconfirmed response. CR, PR and SD were determined by investigators by using RECIST/WHO/clinical evidence as investigators deemed appropriate

3. Progression Free Survival (PFS) [From first administration of the trial drug until objective tumour progression or death, up to 48 months.]

   PFS was measured from start of therapy until progression or death, whichever came first. Progression was defined as the minimum of the first examination with progression and the date of progression documented by the treating physician. One day was added to the corresponding date. Patients without documented progression and not known to have died were censored at their date of last examination and one day was added. Median was derived by Kaplan Meier methods.

4. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From first administration of the trial drug until 30 days end after permanent discontinuation of therapy or end of study, up to 48 months.]

   Percentage of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs).

5. Toxicity and Side-effect Profile: Incidence of Diarrhea, Skin Reactions, Stomatitis and Paronychia [From first administration of the trial drug until 30 days end after permanent discontinuation of therapy or end of study, up to 48 months.]

   Toxicity and side-effect profile: incidence of diarrhea, skin reactions, stomatitis and paronychia. Skin reactions: acne, dermatitis acneiform, dry skin, pruritus, rash, rash maculo-papular, rash pustular.

6. Treatment Duration [From the initial dose of study drug until end of the treatment period, up to 48 months.]

   Duration of treatment with afatinib is calculated as Date of last administration + 1 day - Date of first administration.

7. Symptom Control - Time to Worsening (Cough, Dyspnea and Pain) [Up to 48 months]

   Symptom control was evaluated for cough, dyspnea and pain. Time to deterioration was calculated from date of baseline European Organisation for Research and Treatment of Cancer (EORTC) questionnaire until date of the EORTC questionnaire, where the first deterioration was measured. Patients without deterioration were censored at their date of last answered EORTC questionnaire, where the corresponding scale is evaluable. Participants had to select one answer on a scale ranging from 1=Not at All to 4=Very Much for questions 1 to 28 and 31 to 43 and on scale ranging from 1=Very Bad to 7=Excellent for questions 29 and 30. Afterwards, these scale scores were linearly transformed such that all scales ranged from 0 to 100, where higher scores represented higher level of symptoms.

8. Percentage of Participants With Treatment Modification [From the initial dose of study drug until end of the treatment period, up to 48 months.]

   Percentage of participants with treatment modification was calculated as percentage of participants with any dose reduction, dose escalation or any modification.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• EGFR- tyrosine kinase inhibitor (TKI) naive patients with histologically confirmed locally advanced or metastatic NSCLC with activating EGFR-mutations

• Age >= 18 years

• No diagnostic or therapeutic measures beyond routine clinical practice are required

• Patients for whom the treating physician has decided to initiate treatment with GIOTRIF

• Written informed consent prior inclusion

Exclusion criteria:

• Contraindication for Afatinib according to the Summary of Product characteristics

• Participation in another clinical study until 30 days after end of treatment

• Prior systemic chemotherapy (Neo-/adjuvant therapy is permitted)

• Previous treatment with an EGFR-tyrosine kinase inhibitor

• Patients not willing or not able to fill in quality of life questionnaires

• Patients with missing or impaired legal capacity

• Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Multiple Locations		Germany

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 5, 2017
• Study Protocol - Jul 1, 2014

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02047903
• Other Study ID Numbers: 1200.205
• First Posted: Jan 28, 2014
• Last Update Posted: Jan 9, 2020
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Afatinib

Study Results

Participant Flow

Recruitment Details	This is a non-interventional study (NIS) in real life clinical setting, in which responses were determined by using Response Evaluation Criteria in Solid Tumors (RECIST)/World Health Organization (WHO)/clinical evidence as investigators deemed appropriate.
Pre-assignment Detail	Data source for this study were medical records usually collected during routine clinical practice other than study-specific questionnaires. Data collection was performed between March 24, 2014 and March 14, 2019.

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Period Title: Overall Study
STARTED	161
Treated	152
COMPLETED	102
NOT COMPLETED	59

Baseline Characteristics

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Overall Participants	152
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.32 (10.70)
Sex: Female, Male (Count of Participants)
Female	106 69.7%
Male	46 30.3%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Rate After 12 Months
Description	The rate (probability) of being progression free after 12 months. PFS is defined as the time from first administration of the trial drug until objective tumor progression or death. The rate is the Kaplan-Meier estimated percent probability.
Time Frame	After 12 months

Outcome Measure Data

Analysis Population Description

Per protocol set (PPS): This set included all patients who gave their informed consent, did not violate any inclusion or exclusion criterion and have at least one documented administration of afatinib.

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	146
Number (95% Confidence Interval) [Percent probability of PFS]	50.24

2. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Objective response rate is calculated as a percentage of participants with complete response (CR) or partial response (PR) (i.e CR+PR) as best unconfirmed response. Here CR and PR were determined by investigators by using RECIST/WHO/clinical evidence as investigators deemed appropriate.
Time Frame	From the initial dose of study drug until end of the treatment period, up to 48 months.

Outcome Measure Data

Analysis Population Description

PPS

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	146
Number (95% Confidence Interval) [Percentage of participants]	74.58 49.1%

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Percentage of participants with controlled disease (CR + PR + stable disease (SD)) as best unconfirmed response. CR, PR and SD were determined by investigators by using RECIST/WHO/clinical evidence as investigators deemed appropriate
Time Frame	From the initial dose of study drug until end of the treatment period, up to 48 months.

Outcome Measure Data

Analysis Population Description

PPS

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	146
Number (95% Confidence Interval) [Percentage of participants]	91.53 60.2%

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was measured from start of therapy until progression or death, whichever came first. Progression was defined as the minimum of the first examination with progression and the date of progression documented by the treating physician. One day was added to the corresponding date. Patients without documented progression and not known to have died were censored at their date of last examination and one day was added. Median was derived by Kaplan Meier methods.
Time Frame	From first administration of the trial drug until objective tumour progression or death, up to 48 months.

Outcome Measure Data

Analysis Population Description

PPS

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	146
Median (95% Confidence Interval) [Months]	12.17

5. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	Percentage of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs).
Time Frame	From first administration of the trial drug until 30 days end after permanent discontinuation of therapy or end of study, up to 48 months.

Outcome Measure Data

Analysis Population Description

Treated set (TS): This patient set included all patients who received at least one dose of afatinib.

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	152
AEs	96.05 63.2%
SAEs	42.76 28.1%

6. Secondary Outcome

Title	Toxicity and Side-effect Profile: Incidence of Diarrhea, Skin Reactions, Stomatitis and Paronychia
Description	Toxicity and side-effect profile: incidence of diarrhea, skin reactions, stomatitis and paronychia. Skin reactions: acne, dermatitis acneiform, dry skin, pruritus, rash, rash maculo-papular, rash pustular.
Time Frame	From first administration of the trial drug until 30 days end after permanent discontinuation of therapy or end of study, up to 48 months.

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	152
Diarrhea	82.89 54.5%
Stomatitis	18.42 12.1%
Paronychia	25.66 16.9%
Dermatitis acneiform	37.50 24.7%
Acne	1.32 0.9%
Dry skin	16.45 10.8%
Pruritus	10.53 6.9%
Rash	5.26 3.5%
Rash maculo-papular	17.76 11.7%
Rash pustular	6.58 4.3%

7. Secondary Outcome

Title	Treatment Duration
Description	Duration of treatment with afatinib is calculated as Date of last administration + 1 day - Date of first administration.
Time Frame	From the initial dose of study drug until end of the treatment period, up to 48 months.

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	152
Median (Full Range) [Days]	324.5

8. Secondary Outcome

Title	Symptom Control - Time to Worsening (Cough, Dyspnea and Pain)
Description	Symptom control was evaluated for cough, dyspnea and pain. Time to deterioration was calculated from date of baseline European Organisation for Research and Treatment of Cancer (EORTC) questionnaire until date of the EORTC questionnaire, where the first deterioration was measured. Patients without deterioration were censored at their date of last answered EORTC questionnaire, where the corresponding scale is evaluable. Participants had to select one answer on a scale ranging from 1=Not at All to 4=Very Much for questions 1 to 28 and 31 to 43 and on scale ranging from 1=Very Bad to 7=Excellent for questions 29 and 30. Afterwards, these scale scores were linearly transformed such that all scales ranged from 0 to 100, where higher scores represented higher level of symptoms.
Time Frame	Up to 48 months

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	152
Cough	33.85
Dyspnea	22.17
Pain	18.26

9. Secondary Outcome

Title	Percentage of Participants With Treatment Modification
Description	Percentage of participants with treatment modification was calculated as percentage of participants with any dose reduction, dose escalation or any modification.
Time Frame	From the initial dose of study drug until end of the treatment period, up to 48 months.

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
Measure Participants	152
Any dose reduction	59.87 39.4%
Dose increase	17.11 11.3%
Any dose modifications	61.84 40.7%

Adverse Events

Time Frame	From first administration of the trial drug until 30 days end after permanent discontinuation of therapy or end of study, up to 48 months.
Arm/Group Title	Afatinib
Arm/Group Description	Participants with locally advanced and /or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations received orally 40 milligram (mg) or less than 40 mg Afatinib starting dose once daily as first-line therapy. With dose escalation to maximum of 50 mg/day and reduction to 30 mg/day or 20 mg/day according to the summary of product characteristics (SmPC) under routine clinical conditions. The dose should not be escalated in any participant with a prior dose reduction.
All Cause Mortality
	Afatinib
	Affected / at Risk (%)	# Events
Total	73/152 (48%)
Serious Adverse Events
	Afatinib
	Affected / at Risk (%)	# Events
Total	65/152 (42.8%)
Blood and lymphatic system disorders
Anaemia	2/152 (1.3%)
Thrombotic thrombocytopenic purpura	1/152 (0.7%)
Cardiac disorders
Acute myocardial infarction	1/152 (0.7%)
Cardiac failure	1/152 (0.7%)
Mitral valve disease	1/152 (0.7%)
Myocardial infarction	1/152 (0.7%)
Ear and labyrinth disorders
Vertigo	2/152 (1.3%)
Eye disorders
Cataract	1/152 (0.7%)
Vision blurred	1/152 (0.7%)
Gastrointestinal disorders
Abdominal pain	1/152 (0.7%)
Anal haemorrhage	1/152 (0.7%)
Diarrhea	22/152 (14.5%)
Gastric haemorrhage	1/152 (0.7%)
Gastritis	2/152 (1.3%)
Ileus	2/152 (1.3%)
Nausea	4/152 (2.6%)
Pancreatitis	1/152 (0.7%)
Stomatitis	1/152 (0.7%)
Vomiting	3/152 (2%)
General disorders
Chest pain	1/152 (0.7%)
Death	2/152 (1.3%)
General physical health deterioration	3/152 (2%)
Pyrexia	2/152 (1.3%)
Hepatobiliary disorders
Pneumobilia	1/152 (0.7%)
Infections and infestations
Arthritis infective	1/152 (0.7%)
Biliary tract infection	1/152 (0.7%)
Cystitis	1/152 (0.7%)
Enteritis infectious	1/152 (0.7%)
Intervertebral discitis	1/152 (0.7%)
Lung infection	4/152 (2.6%)
Osteomyelitis	1/152 (0.7%)
Pneumonia	1/152 (0.7%)
Sepsis	1/152 (0.7%)
Skin infection	1/152 (0.7%)
Soft tissue infection	1/152 (0.7%)
Urinary tract infection	1/152 (0.7%)
Viral infection	1/152 (0.7%)
Injury, poisoning and procedural complications
Fall	1/152 (0.7%)
Fracture	1/152 (0.7%)
Hip fracture	1/152 (0.7%)
Overdose	1/152 (0.7%)
Spinal fracture	1/152 (0.7%)
Investigations
Amylase increased	1/152 (0.7%)
Blood creatinine increased	1/152 (0.7%)
Lipase increased	1/152 (0.7%)
Metabolism and nutrition disorders
Decreased appetite	1/152 (0.7%)
Dehydration	4/152 (2.6%)
Hyperkalaemia	1/152 (0.7%)
Hypokalaemia	2/152 (1.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/152 (0.7%)
Muscle spasms	1/152 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/152 (0.7%)
Malignant neoplasm progression	1/152 (0.7%)
Metastases to bone	1/152 (0.7%)
Metastases to central nervous system	1/152 (0.7%)
Oesophageal carcinoma	1/152 (0.7%)
Prostate cancer	1/152 (0.7%)
Squamous cell carcinoma	1/152 (0.7%)
Nervous system disorders
Cerebral ischaemia	1/152 (0.7%)
Cerebrovascular accident	2/152 (1.3%)
Dizziness	1/152 (0.7%)
Dysarthria	1/152 (0.7%)
Hemiparesis	1/152 (0.7%)
Seizure	1/152 (0.7%)
Psychiatric disorders
Depression	1/152 (0.7%)
Renal and urinary disorders
Acute kidney injury	3/152 (2%)
Renal colic	1/152 (0.7%)
Renal failure	1/152 (0.7%)
Urinary retention	1/152 (0.7%)
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction	1/152 (0.7%)
Dyspnoea	5/152 (3.3%)
Haemoptysis	2/152 (1.3%)
Pleural effusion	7/152 (4.6%)
Pneumothorax	1/152 (0.7%)
Pulmonary embolism	1/152 (0.7%)
Respiratory failure	1/152 (0.7%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	2/152 (1.3%)
Dermatitis bullous	1/152 (0.7%)
Dermatitis exfoliative generalised	1/152 (0.7%)
Stevens-Johnson syndrome	1/152 (0.7%)
Surgical and medical procedures
Spinal operation	1/152 (0.7%)
Vascular disorders
Embolism	5/152 (3.3%)
Hypertensive crisis	1/152 (0.7%)
Other (Not Including Serious) Adverse Events
	Afatinib
	Affected / at Risk (%)	# Events
Total	144/152 (94.7%)
Gastrointestinal disorders
Abdominal pain	12/152 (7.9%)
Diarrhea	123/152 (80.9%)
Nausea	20/152 (13.2%)
Stomatitis	28/152 (18.4%)
Vomiting	13/152 (8.6%)
General disorders
Fatigue	23/152 (15.1%)
Influenza like illness	8/152 (5.3%)
Infections and infestations
Nail infection	10/152 (6.6%)
Paronychia	42/152 (27.6%)
Rash pustular	10/152 (6.6%)
Investigations
Weight decreased	9/152 (5.9%)
Metabolism and nutrition disorders
Decreased appetite	11/152 (7.2%)
Respiratory, thoracic and mediastinal disorders
Cough	8/152 (5.3%)
Dyspnoea	9/152 (5.9%)
Skin and subcutaneous tissue disorders
Alopecia	24/152 (15.8%)
Dermatitis acneiform	58/152 (38.2%)
Dermatitis exfoliative generalised	8/152 (5.3%)
Dry skin	28/152 (18.4%)
Pruritus	16/152 (10.5%)
Rash	8/152 (5.3%)
Rash maculo-papular	27/152 (17.8%)
Skin fissures	8/152 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.