Trial Outcomes & Findings for Efficacy and Safety of Nintedanib Co-administered With Sildenafil in Idiopathic Pulmonary Fibrosis Patients With Advanced Lung Function Impairment (NCT NCT02802345)

Last Updated: 2019-01-11

Results Overview

The SGRQ is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Scores range from 0 to 100, with higher scores indicating more limitations. The mean and standard error presented are actually adjusted mean for change from baseline and its standard error.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

274 participants

Primary outcome timeframe

Baseline and week 12

Results posted on

2019-01-11

Participant Flow

Randomised, double-blind, parallel design comparison of nintedanib 150 milligram (mg) twice daily (bid) and sildenafil 20 mg three times a day (tid) to nintedanib 150 mg bid and placebo matching sildenafil tid administered orally over 24 weeks.

All patients were screened for eligibility to participate in the trial. Patients attended specialist sites to ensure that all patients met all inclusion/exclusion criteria. Patients were not to be randomized to trial if any one of the specific entry criteria were not met.

Participant milestones

Participant milestones
Measure	Nintedanib+Placebo Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Overall Study STARTED	136	138
Overall Study Treated	136	137
Overall Study COMPLETED	104	108
Overall Study NOT COMPLETED	32	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Nintedanib+Placebo Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Overall Study Not Treated	0	1
Overall Study Adverse Event	28	20
Overall Study Withdrawal by Subject	3	3
Overall Study Protocol Violation	0	1
Overall Study Other than listed	1	5

Baseline Characteristics

Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nintedanib+Placebo n=136 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil n=137 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.	Total n=273 Participants Total of all reporting groups
Age, Continuous	70.0 Years STANDARD_DEVIATION 7.9 • n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	70.3 Years STANDARD_DEVIATION 8.6 • n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	70.1 Years STANDARD_DEVIATION 8.2 • n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Sex: Female, Male Female	30 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	27 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	57 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Sex: Female, Male Male	106 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	110 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	216 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	23 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	38 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	114 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	235 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	3 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	5 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Race (NIH/OMB) Asian	39 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	30 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	69 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Race (NIH/OMB) White	95 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	103 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	198 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	1 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	1 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=7 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.	0 Participants n=5 Participants • Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.

PRIMARY outcome

Timeframe: Baseline and week 12

Population: TS

Outcome measures

Outcome measures
Measure	Nintedanib+Placebo n=133 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil n=132 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score at Week 12	-0.77 Unit on scale Standard Error 1.009	-1.28 Unit on scale Standard Error 1.013

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Treated Set (TS): TS included all patients who were randomised to a treatment group and received at least one dose of randomised study medication.

The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.

Outcome measures

Outcome measures
Measure	Nintedanib+Placebo n=122 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil n=120 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Change From Baseline in Dyspnoea Using the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) at Week 12	4.40 Unit on scale Standard Deviation 1.529	1.46 Unit on scale Standard Deviation 1.575

SECONDARY outcome

Timeframe: Baseline and week 24

Population: TS

The SGRQ is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.

Outcome measures

Outcome measures
Measure	Nintedanib+Placebo n=133 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil n=132 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Change From Baseline in SGRQ Total Score at Week 24	2.42 Unit on scale Standard Deviation 1.158	0.23 Unit on scale Standard Deviation 1.148

SECONDARY outcome

Timeframe: Baseline and week 24

Population: TS

The UCSD SOBQ is a 24-item questionnaire developed to to measure breathlessness on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.

Outcome measures

Outcome measures
Measure	Nintedanib+Placebo n=124 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil n=123 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Change From Baseline in Dyspnoea Using UCSD SOBQ at Week 24	6.85 Unit on scale Standard Deviation 1.791	4.44 Unit on scale Standard Deviation 1.779

SECONDARY outcome

Timeframe: Baseline and week 24

Population: TS

Percentage of patients with on-treatment serious adverse events (SAE) from baseline to Week 24 is presented.

Outcome measures

Outcome measures
Measure	Nintedanib+Placebo n=136 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil n=137 Participants Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Percentage of Patients With On-treatment Serious Adverse Events (SAE) From Baseline to Week 24	32.4 Percentage of participants (%)	27.0 Percentage of participants (%)

Adverse Events

Nintedanib+Placebo

Serious events: 44 serious events

Other events: 113 other events

Deaths: 12 deaths

Nintedanib+Sildenafil

Serious events: 37 serious events

Other events: 118 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim, Call Centre

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Nintedanib+Placebo n=136 participants at risk Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with placebo matching to Sildenafil for 24 weeks.	Nintedanib+Sildenafil n=137 participants at risk Patients administered 150 milligram (mg) soft gelatine capsule orally twice daily (bid), with a possibility of dose reduction to 100 mg capsule bid along with 20 mg thrice daily (tid) Sildenafil for 24 weeks.
Gastrointestinal disorders Abdominal pain	6.6% 9/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	2.9% 4/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Gastrointestinal disorders Abdominal pain upper	5.1% 7/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	4.4% 6/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Gastrointestinal disorders Constipation	5.9% 8/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	2.2% 3/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Gastrointestinal disorders Diarrhoea	48.5% 66/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	57.7% 79/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Gastrointestinal disorders Dyspepsia	2.9% 4/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	6.6% 9/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.7% 5/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.1% 7/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Gastrointestinal disorders Nausea	10.3% 14/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	16.1% 22/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Gastrointestinal disorders Vomiting	6.6% 9/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	13.9% 19/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
General disorders Asthenia	5.1% 7/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	4.4% 6/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
General disorders Fatigue	4.4% 6/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.1% 7/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
General disorders Oedema peripheral	4.4% 6/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.1% 7/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
General disorders Pyrexia	6.6% 9/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	4.4% 6/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Infections and infestations Bronchitis	2.9% 4/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	8.8% 12/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Infections and infestations Influenza	5.1% 7/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	2.9% 4/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Infections and infestations Nasopharyngitis	5.9% 8/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	6.6% 9/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Infections and infestations Respiratory tract infection	2.9% 4/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.8% 8/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Investigations Alanine aminotransferase increased	5.9% 8/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.8% 8/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Investigations Aspartate aminotransferase increased	5.1% 7/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	3.6% 5/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Investigations C-reactive protein increased	5.1% 7/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	4.4% 6/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Investigations Gamma-glutamyltransferase increased	5.1% 7/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.1% 7/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Investigations Weight decreased	8.8% 12/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.1% 7/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Metabolism and nutrition disorders Decreased appetite	16.9% 23/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	13.9% 19/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Musculoskeletal and connective tissue disorders Back pain	1.5% 2/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.1% 7/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Musculoskeletal and connective tissue disorders Myalgia	2.2% 3/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	5.1% 7/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Nervous system disorders Dizziness	5.9% 8/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	4.4% 6/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Nervous system disorders Headache	7.4% 10/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	15.3% 21/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Respiratory, thoracic and mediastinal disorders Cough	9.6% 13/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	14.6% 20/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.1% 11/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	9.5% 13/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.4% 6/136 • From first drug administration to 28 days after the last trial medication administration, 227 days.	8.0% 11/137 • From first drug administration to 28 days after the last trial medication administration, 227 days.