Trial Outcomes & Findings for BI 113608 Administered as Tablets Twice Daily Over 4 Weeks in Patients With Chronic Obstructive Pulmonary Disease Associated With Chronic Bronchitis (NCT NCT01958008)

NCT ID: NCT01958008

Last Updated: 2017-01-20

Results Overview

Number (%) of patients with drug-related adverse events (AEs)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

84 participants

Primary outcome timeframe

AE's occuring upto end of treatment + 3 days follow up (Up to 31 days)

Results posted on

2017-01-20

Participant Flow

The trial consisted of 3 sequential dose groups of 28 patients each. Within each dose group, 21 patients received BI 113608 and 7 received placebo

Participant milestones

Participant milestones
Measure	Placebo Oral administration of Placebo matching BI 113608	BI 113608 10 mg Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
Overall Study STARTED	21	21	21	21
Overall Study COMPLETED	20	21	20	21
Overall Study NOT COMPLETED	1	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Oral administration of Placebo matching BI 113608	BI 113608 10 mg Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
Overall Study Worsening of disease under study	0	0	1	0
Overall Study Other adverse event	1	0	0	0

Baseline Characteristics

BI 113608 Administered as Tablets Twice Daily Over 4 Weeks in Patients With Chronic Obstructive Pulmonary Disease Associated With Chronic Bronchitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=21 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=21 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg n=21 Participants Oral administration of BI 113608 50 mg film coated tablets twice daily	Total n=84 Participants Total of all reporting groups
Age, Continuous	60.67 years STANDARD_DEVIATION 6.64 • n=5 Participants	58.90 years STANDARD_DEVIATION 6.17 • n=7 Participants	62.43 years STANDARD_DEVIATION 7.21 • n=5 Participants	60.38 years STANDARD_DEVIATION 6.81 • n=4 Participants	60.60 years STANDARD_DEVIATION 6.71 • n=21 Participants
Gender Female	8 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	34 Participants n=21 Participants
Gender Male	13 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	13 Participants n=4 Participants	50 Participants n=21 Participants

PRIMARY outcome

Timeframe: AE's occuring upto end of treatment + 3 days follow up (Up to 31 days)

Population: Treated set (TS)

Number (%) of patients with drug-related adverse events (AEs)

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=21 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=21 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg n=21 Participants Oral administration of BI 113608 50 mg film coated tablets twice daily
Number (%) of Patients With Drug-related Adverse Events (AEs)	7 percentage of participants	7 percentage of participants	10 percentage of participants	14 percentage of participants

SECONDARY outcome

Timeframe: Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration

Population: Pharmacokinetic set (PKS): The patient set for the evaluation of PK endpoints included all evaluable patients in the treated set which provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of PK.

Cmax,ss (maximum measured concentration of BI 113608 in plasma at steady state over a uniform dosing interval tau)

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=20 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=20 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
Cmax,ss	44.1 nmol/L Geometric Coefficient of Variation 66.6	190 nmol/L Geometric Coefficient of Variation 45.1	328 nmol/L Geometric Coefficient of Variation 49.5	—

SECONDARY outcome

Population: PKS

AUC tau,ss (area under the concentration-time curve of the BI 113608 in plasma at steady state over a uniform dosing interval tau)

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=20 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=20 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
AUC Tau,ss	166 nmol*h/L Geometric Coefficient of Variation 46.4	539 nmol*h/L Geometric Coefficient of Variation 43.3	1160 nmol*h/L Geometric Coefficient of Variation 42.3	—

SECONDARY outcome

Population: PKS

Tmax,ss (time from last dosing to maximum concentration of the BI 113608 in plasma at steady state)

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=20 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=20 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
Tmax,ss	1.00 hours Interval 0.5 to 2.03	0.750 hours Interval 0.5 to 2.0	1.00 hours Interval 0.5 to 3.0	—

SECONDARY outcome

Population: PKS

T1/2,ss (terminal half life of the BI 113608 in plasma at steady state)

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=20 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=20 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
T1/2,ss	17.4 hours Geometric Coefficient of Variation 32.2	15.2 hours Geometric Coefficient of Variation 14.9	16.2 hours Geometric Coefficient of Variation 31.5	—

SECONDARY outcome

Population: PKS

R(A,Cmax) (accumulation ratio of the BI 113608 in plasma at steady state after multiple oral administration over a uniform dosing interval tau, expressed as ratio of Cmax at steady state and after first dose)

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=20 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=20 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
R(A,Cmax)	1.36 ratio Geometric Coefficient of Variation 56.6	0.98 ratio Geometric Coefficient of Variation 42.2	1.13 ratio Geometric Coefficient of Variation 42.2	—

SECONDARY outcome

Population: PKS

R(A,AUC) (accumulation ratio of the BI 113608 in plasma at steady state after multiple oral administration over a uniform dosing interval tau, expressed as ratio of AUC at steady state and after first dose)

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Oral administration of Placebo matching BI 113608	BI 113608 10 mg n=20 Participants Oral administration of BI 113608 10 mg film coated tablets twice daily	BI 113608 25 mg n=20 Participants Oral administration of BI 113608 25 mg film coated tablets twice daily	BI 113608 50 mg Oral administration of BI 113608 50 mg film coated tablets twice daily
R(A,AUC)	1.40 ratio Geometric Coefficient of Variation 35.8	1.20 ratio Geometric Coefficient of Variation 31.4	1.37 ratio Geometric Coefficient of Variation 27.0	—

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

10 mg Bid

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

25 mg Bid

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

50 mg Bid

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=21 participants at risk Oral administration of Placebo matching BI 113608	10 mg Bid n=21 participants at risk Oral administration of BI 113608 10 mg film coated tablets twice daily	25 mg Bid n=21 participants at risk Oral administration of BI 113608 25 mg film coated tablets twice daily	50 mg Bid n=21 participants at risk Oral administration of BI 113608 50 mg film coated tablets twice daily
Cardiac disorders Angina pectoris	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Investigations Blood potassium increased	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 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	Placebo n=21 participants at risk Oral administration of Placebo matching BI 113608	10 mg Bid n=21 participants at risk Oral administration of BI 113608 10 mg film coated tablets twice daily	25 mg Bid n=21 participants at risk Oral administration of BI 113608 25 mg film coated tablets twice daily	50 mg Bid n=21 participants at risk Oral administration of BI 113608 50 mg film coated tablets twice daily
Infections and infestations Nasopharyngitis	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	14.3% 3/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Infections and infestations Conjunctivitis	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Infections and infestations Rhinitis	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Nervous system disorders Headache	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	19.0% 4/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	19.0% 4/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	28.6% 6/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Respiratory, thoracic and mediastinal disorders Cough	19.0% 4/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	14.3% 3/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Respiratory, thoracic and mediastinal disorders Sputum increased	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	14.3% 3/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Gastrointestinal disorders Diarrhoea	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	14.3% 3/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	14.3% 3/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	23.8% 5/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Gastrointestinal disorders Nausea	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	14.3% 3/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Gastrointestinal disorders Abdominal pain upper	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Gastrointestinal disorders Constipation	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Gastrointestinal disorders Dry mouth	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Gastrointestinal disorders Vomiting	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Skin and subcutaneous tissue disorders Dry skin	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Musculoskeletal and connective tissue disorders Back pain	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	0.00% 0/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	9.5% 2/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period	4.8% 1/21 • From the first drug administration until 3 days after last study drug administration, up to 31 days. The above mentioned time frame corresponds to AEs that occurred during on treatment period