Multiple Rising Oral Doses of BI 691751 in Healthy Male Subjects

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02148107
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 7
• Duration (Months): 3
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

It is the objective of this MRD trial to investigate pharmacokinetics, pharmcodynamics, safety and tolerability of rising doses BI 691751 over a treatment period of 14 days to support the further clinical development of this LTA4H-inhibitor. Special emphasis will be given to detect potential effects of BI 691751 on heart rate.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: BI 691751; Drug: BI 691751; Drug: BI 691751; Drug: BI 691751; Drug: BI 691751; Drug: BI 691751; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 691751 in Healthy Male Subjects
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 691751 Dose 1 multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 1
Experimental: BI 691751 Dose 2 multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 2
Experimental: BI 691751 Dose 3 multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 3
Experimental: BI 691751 Dose 4 multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 4
Experimental: BI 691751 Dose 5 multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 5
Experimental: BI 691751 Dose 6 multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 6
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Drug-related Adverse Events [From the time of administration of the respective treatment until 21 days after last administration of study drug or start of the post-study phase to the respective treatment, up to 35 days]

   Percentage of subjects with drug-related Adverse events (AEs)

Secondary Outcome Measures

1. AUCt,1 (Area Under the Concentration-time Curve of the Analyte in Plasma Over a Uniform Dosing Interval t After Administration of the First Dose) [0 minutes (min), 10min, 20min, 40min, 1 hour (h), 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h after first drug administration]

   AUCt,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval t after administration of the first dose). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.

2. Cmax (Maximum Measured Concentration of the Analyte Inplasma) [0 minutes (min), 10min, 20min, 40min, 1 hour (h), 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h after first drug administration]

   Cmax (maximum measured concentration of the analyte inplasma). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.

3. AUCt,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t) [312 hours (h), 312 h 10 minutes (min), 312h 20min, 312h 40min, 313, 313h 30min, 314h, 315h, 316h, 318h, 320h, 322h, 324h and 336h after first drug administration]

   AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.

4. Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t) [312 hours (h), 312 h 10 minutes (min), 312h 20min, 312h 40min, 313, 313h 30min, 314h, 315h, 316h, 318h, 320h, 322h, 324h and 336h after first drug administration]

   Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• Healthy male subjects according to the investigator´s assessment, based on a complete medical history including a physical examination, vital signs (BP (blood pressure), PR (pulse rate), 12-lead ECG (electro cardiogramm), and clinical laboratory tests

• Age of 18 to 50 years (incl.)

• BMI (body mass index) of 18.5 to 29.9 kg/m2 (incl.)

• Signed and dated written informed consent prior to admission to the study in accordance with GCP(Good Clinical Practice) and local legislation

• Subject is able to understand and communicate in German

Exclusion criteria:

• Any finding in the medical examination (including BP (blood pressure), PR (pulse rate) or ECG (electro cardiogramm) is deviating from normal and judged as clinically relevant by the investigator

• Pulse rate outside 45-80 bpm (beats per minutes) or repeated measurement of systolic blood pressure greater than 140 mmHg, diastolic blood pressure greater than 90 mm Hg

• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance

• Any evidence of a concomitant disease judged as clinically relevant by the investigator

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

• Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication

• Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders

• History of relevant orthostatic hypotension, fainting spells, or blackouts

• Chronic or relevant acute infections

• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)

• Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication

• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval

• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication

• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)

• Inability to refrain from smoking during inhouse-confinement

• Alcohol abuse (consumption of more 30 g per day for males)

• Drug abuse or positive drug screening

• Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial

• Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial

• Inability to comply with dietary regimen of trial site

• A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant ECG finding at screening

• A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)

• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

• Vulnerable subjects, e.g. subjects kept in detention, soldiers, employees of the sponsor or a clinical research organization, involved in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1334.2.1 Boehringer Ingelheim Investigational Site	Berlin		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

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02148107
• Other Study ID Numbers: 1334.2; 2013-003813-17
• First Posted: May 28, 2014
• Last Update Posted: Feb 29, 2016
• Last Verified: Feb 1, 2016

Study Results

Participant Flow

Recruitment Details	The trial was terminated early therefore only the first 2 dose levels planned (0.5 mg and 3.0 mg) were administered. In addition, due to recruitment problems fewer subjects than planned were randomised into the placebo and BI 691751 3mg groups.

Arm/Group Title	BI 691751 0.5mg	BI 691751 3mg	Placebo
Arm/Group Description	Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days	Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.	Oral administration of a placebo tablet matching the BI 691751 tablets, taken once daily for 14 days.
Period Title: Overall Study
STARTED	8	7	3
COMPLETED	8	7	3
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	BI 691751 0.5mg	BI 691751 3mg	Placebo	Total
Arm/Group Description	Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days	Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.	Oral administration of a placebo tablet matching the BI 691751 tablets, taken once daily for 14 days.	Total of all reporting groups
Overall Participants	8	7	3	18
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	33.5 (5.9)	29.7 (2.8)	33.3 (2.1)	32.0 (4.6)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	8 100%	7 100%	3 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Drug-related Adverse Events
Description	Percentage of subjects with drug-related Adverse events (AEs)
Time Frame	From the time of administration of the respective treatment until 21 days after last administration of study drug or start of the post-study phase to the respective treatment, up to 35 days

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	BI 691751 0.5mg	BI 691751 3mg	Placebo
Arm/Group Description	Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days	Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.	Oral administration of a placebo tablet matching the BI 691751 tablets, taken once daily for 14 days.
Measure Participants	8	7	3
Number [Percentage of participants]	0 0%	28.6 408.6%	0 0%

2. Secondary Outcome

Title	AUCt,1 (Area Under the Concentration-time Curve of the Analyte in Plasma Over a Uniform Dosing Interval t After Administration of the First Dose)
Description	AUCt,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval t after administration of the first dose). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.
Time Frame	0 minutes (min), 10min, 20min, 40min, 1 hour (h), 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h after first drug administration

Outcome Measure Data

Analysis Population Description

PK set. As no PK blood samples were analysed due to the early termination of the study, no PK parameters could be calculated and so the PK set contains 0 participants.

Arm/Group Title	BI 691751 0.5mg	BI 691751 3mg
Arm/Group Description	Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days	Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.
Measure Participants	0	0

3. Secondary Outcome

Title	Cmax (Maximum Measured Concentration of the Analyte Inplasma)
Description	Cmax (maximum measured concentration of the analyte inplasma). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.
Time Frame	0 minutes (min), 10min, 20min, 40min, 1 hour (h), 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h after first drug administration

Outcome Measure Data

Analysis Population Description

PK set. As no PK blood samples were analysed due to the early termination of the study, no PK parameters could be calculated and so the PK set contains 0 participants.

Arm/Group Title	BI 691751 0.5mg	BI 691751 3mg
Arm/Group Description	Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days	Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.
Measure Participants	0	0

4. Secondary Outcome

Title	AUCt,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t)
Description	AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.
Time Frame	312 hours (h), 312 h 10 minutes (min), 312h 20min, 312h 40min, 313, 313h 30min, 314h, 315h, 316h, 318h, 320h, 322h, 324h and 336h after first drug administration

Outcome Measure Data

Analysis Population Description

PK set. As no PK blood samples were analysed due to the early termination of the study, no PK parameters could be calculated and so the PK set contains 0 participants.

Arm/Group Title	BI 691751 0.5mg	BI 691751 3mg
Arm/Group Description	Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days	Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.
Measure Participants	0	0

5. Secondary Outcome

Title	Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t)
Description	Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.
Time Frame	312 hours (h), 312 h 10 minutes (min), 312h 20min, 312h 40min, 313, 313h 30min, 314h, 315h, 316h, 318h, 320h, 322h, 324h and 336h after first drug administration

Outcome Measure Data

Analysis Population Description

PK set. As no PK blood samples were analysed due to the early termination of the study, no PK parameters could be calculated and so the PK set contains 0 participants.

Arm/Group Title	BI 691751 0.5mg	BI 691751 3mg
Arm/Group Description	Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days	Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.
Measure Participants	0	0

Adverse Events

Time Frame	From the time of administration of the respective treatment until 21 days after last administration of study drug or start of the post-study phase to the respective treatment, up to 35 days
Arm/Group Title	Placebo		BI 691751 0.5mg		BI 691751 3mg
Arm/Group Description	Oral administration of a placebo tablet matching the BI 691751 tablets, taken once daily for 14 days.		Oral administration of a BI 691751 0.5mg tablet taken once daily for 14 days		Oral administration of BI 681751 3mg, consisting of two 0.5 mg tablets and a 2mg tablet, taken once daily for 14 days.
All Cause Mortality
	Placebo		BI 691751 0.5mg		BI 691751 3mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		BI 691751 0.5mg		BI 691751 3mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/8 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		BI 691751 0.5mg		BI 691751 3mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		2/8 (25%)		3/7 (42.9%)
Gastrointestinal disorders
Diarrhoea	0/3 (0%)		0/8 (0%)		2/7 (28.6%)
Flatulence	0/3 (0%)		0/8 (0%)		2/7 (28.6%)
General disorders
Chills	0/3 (0%)		0/8 (0%)		1/7 (14.3%)
Malaise	0/3 (0%)		1/8 (12.5%)		0/7 (0%)
Infections and infestations
Nasopharyngitis	0/3 (0%)		0/8 (0%)		2/7 (28.6%)
Rhinitis	1/3 (33.3%)		0/8 (0%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)		0/8 (0%)		1/7 (14.3%)
Nervous system disorders
Headache	1/3 (33.3%)		1/8 (12.5%)		1/7 (14.3%)

Limitations/Caveats

The trial was terminated prematurely because the sponsor decided to discontinue the development of BI 691751, also no PK blood samples were analysed because of the trial termination.

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.