Bioavailability of 3 Different Formulations of BI 207127 in Healthy Male Volunteers

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01535638
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 3

Study Details

Study Description

Brief Summary

The primary objective of the current study is to investigate the relative bioavailability of three trial formulations of BI 207127, the trial formulation 2 (TFII), the final formulation (FF), and a FF modified formulation. All formulations are supplied as film-coated Tablets and administered as single dose treatments of BI 207127 (3 film-coated Tablets) in healthy volunteers, with the aim to compare the bioavailability of the three formulations. All treatments will be applied fed, 30 minutes after start of the intake of a standard normal breakfast.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: BI 207127; Drug: BI 207127; Drug: BI 207127	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Relative Bioavailability of BI 207127 FF Tablets, BI 207127 FF Modified Tablets and BI 207127 TFII Tablets Administered Orally as Three Tablets (Single Dose) to Healthy Male Volunteers, an Open-label, Randomised Three-way Crossover Study
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: BI 207127 NA TFII medium dose Film-coated tablet for oral administration	Drug: BI 207127; Medium dose film-coated tablet
Active Comparator: BI 207127 NA FF medium dose Film-coated tablet for oral administration	Drug: BI 207127; Medium dose film-coated tablet
Active Comparator: BI 207127 NA FF modified medium dose Film-coated tablet for oral administration	Drug: BI 207127; Medium dose film-coated tablet

Outcome Measures

Primary Outcome Measures

1. AUC0-∞ [1:00 (h) hour before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration]

   Area under the concentration-time curve of Deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

2. Cmax [1:00 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration]

   Maximum measured concentration of Deleobuvir in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

1. Healthy males according to a complete medical history, including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests

2. Age =21and Age =50 years

3. Body mass index =18.5 and BMI = 29.9 kg/m2

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

Exclusion criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance

2. Any evidence of a clinically relevant concomitant disease

3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

4. Surgery of the gastrointestinal tract (except appendectomy)

5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders

6. History of relevant orthostatic hypotension, fainting spells or blackouts

7. Chronic or relevant acute infections

8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)

9. Intake of drugs with a long half-life (> 24 hours) within at least 10 half-lifes prior to administration of the trial drug or during the trial

10. Use of drugs which might reasonably influence the results of the trial within 10 days prior to administration or during the trial

11. Participation in another trial with an investigational drug within two months prior to administration of the trial drug or during the trial

12. Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)

13. Alcohol abuse (more than 40 g/day)

14. Drug abuse

15. Blood donation (more than 100 mL within four weeks prior to first administration of the trial drug or during the trial)

16. Excessive physical activities (within one week prior to first administration of the trial drug or during the trial)

17. Any laboratory value outside the reference range that is of clinical relevance

18. Inability to comply with dietary regimen of trial site

19. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)

20. A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

21. History of photosensitivity or recurrent rash

22. Subject is not willing to avoid sun exposure from the first administration of the trial drug until the end of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1241.26.1 Boehringer Ingelheim Investigational Site	Ingelheim		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: NCT01535638
• Other Study ID Numbers: 1241.26
• First Posted: Feb 20, 2012
• Last Update Posted: Apr 11, 2016
• Last Verified: Mar 1, 2016

Study Results

Participant Flow

Arm/Group Title	Trial Formulation II / Final Formulation (FF) / FF Modified	Trial Formulation II / Final Formulation (FF) Modified / FF	Final Formulation (FF) / Trial Formulation II / FF Modified	Final Formulation (FF) / FF Modified / Trial Formulation II	Final Formulation (FF) Modified / Trial Formulation II / FF	Final Formulation (FF) Modified / FF / Trial Formulation II
Arm/Group Description	In this sequence group the treatments (600 mg Deleobuvir in different formulations, single dose) are administered in the order Trial Formulation (TF) II, Final Formulation (FF) and FF modified. There was a wash out period of at least 6 days between each drug administration.	In this sequence group the treatments (600 mg Deleobuvir in different formulations, single dose) are administered in the order Trial Formulation II, Final Formulation modified and Final Formulation. There was a wash out period of at least 6 days between each drug administration.	In this sequence group the treatments (600 mg Deleobuvir in different formulations, single dose) are administered in the order Final Formulation, Trial Formulation II and Final Formulation modified. There was a wash out period of at least 6 days between each drug administration.	In this sequence group the treatments (600 mg Deleobuvir in different formulations, single dose) are administered in the order Final Formulation, Final Formulation modified and Trial Formulation II. There was a wash out period of at least 6 days between each drug administration.	In this sequence group the treatments (600 mg Deleobuvir in different formulations, single dose) are administered in the order Final Formulation modified, Trial Formulation II and Final Formulation. There was a wash out period of at least 6 days between each drug administration.	In this sequence group the treatments (600 mg Deleobuvir in different formulations, single dose) are administered in the order Final Formulation modified, Final Formulation and Trial Formulation II. There was a wash out period of at least 6 days between each drug administration.
Period Title: Treatment 1 (Single Dose)
STARTED	3	3	3	3	3	3
COMPLETED	3	3	3	3	3	2
NOT COMPLETED	0	0	0	0	0	1
Period Title: Treatment 1 (Single Dose)
STARTED	3	3	3	3	3	2
COMPLETED	3	3	3	3	3	2
NOT COMPLETED	0	0	0	0	0	0
Period Title: Treatment 1 (Single Dose)
STARTED	3	3	3	3	3	2
COMPLETED	3	3	3	2	3	2
NOT COMPLETED	0	0	0	1	0	0

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	This study was conducted in healthy male subjects as open-label, single-dose, randomised three-way crossover trial to investigate relative bioavailability. Each subject was planned to receive all 3 treatments in a randomly assigned order. The treatments were 3 single doses of 600 mg (3 film-coated tablets à 200 mg each) of Deleobuvir, either as TF II (trial formulation 2) formulation, FF (final formulation) formulation or as FF modified formulation.
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (6.2)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	18 100%

Outcome Measures

1. Primary Outcome

Title	AUC0-∞
Description	Area under the concentration-time curve of Deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time Frame	1:00 (h) hour before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set (PKS) included all subjects in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK and no vomiting must have occurred at or before two times the median tmax.

Arm/Group Title	Deleobuvir Trial Formulation II	Deleobuvir Final Formulation	Deleobuvir Final Formulation Modified
Arm/Group Description	Trial formulation II film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.	Final formulation film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.	Final formulation modified film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.
Measure Participants	13	15	14
Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L]	10600 (45.0)	12400 (57.3)	13600 (66.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deleobuvir Trial Formulation II, Deleobuvir Final Formulation
	Comments	Relative bioavailability comparison of Deleobuvir Trial Formulation II (reference) and Deleobuvir Final Formulation (test) in pairwise comparison. (reference : test)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (%)
	Estimated Value	123.4
	Confidence Interval	(2-Sided) 90%; 108.0 to 141.1
	Parameter Dispersion	Type: Standard Deviation; Value: 17.1
	Estimation Comments	The estimate of the relative bioavailability (%) is adjusted for the period effects in the ANOVA. The standard deviation is actually the gCV. CIs are based on the residual error from ANOVA, considering only the data from the 2 compared treatments.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deleobuvir Final Formulation, Deleobuvir Final Formulation Modified
	Comments	relative bioavailability comparison of Deleobuvir Final Formulation modified (test) and Deleobuvir Final Formulation (reference) in pairwise comparison. (reference : test)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (%)
	Estimated Value	109.8
	Confidence Interval	(2-Sided) 90%; 88.6 to 136.1
	Parameter Dispersion	Type: Standard Deviation; Value: 28.8
	Estimation Comments	The estimate of the relative bioavailability (%) is adjusted for the period effects in the ANOVA. The standard deviation is actually the gCV. CIs are based on the residual error from ANOVA, considering only the data from the 2 compared treatments.

2. Primary Outcome

Title	Cmax
Description	Maximum measured concentration of Deleobuvir in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time Frame	1:00 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set (PKS).

Arm/Group Title	Deleobuvir Trial Formulation II	Deleobuvir Final Formulation	Deleobuvir Final Formulation Modified
Arm/Group Description	Trial formulation II film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.	Final formulation film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.	Final formulation modified film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.
Measure Participants	13	15	14
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	2460 (48.3)	2990 (53.6)	3070 (73.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deleobuvir Trial Formulation II, Deleobuvir Final Formulation
	Comments	relative bioavailability comparison of Deleobuvir Final Formulation (test) and Deleobuvir Trial Formulation II (reference) in pairwise comparison. (test : reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (%)
	Estimated Value	122.5
	Confidence Interval	(2-Sided) 90%; 107.9 to 139.1
	Parameter Dispersion	Type: Standard Deviation; Value: 16.1
	Estimation Comments	The estimate of the relative bioavailability (%) is adjusted for the period effects in the ANOVA. The standard deviation is actually the gCV. CIs are based on the residual error from ANOVA, considering only the data from the 2 compared treatments.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deleobuvir Final Formulation, Deleobuvir Final Formulation Modified
	Comments	relative bioavailability comparison of Deleobuvir Final Formulation modified (test) and Deleobuvir Final Formulation (reference) in pairwise comparison. (test : reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (%)
	Estimated Value	107.6
	Confidence Interval	(2-Sided) 90%; 83.1 to 139.4
	Parameter Dispersion	Type: Standard Deviation; Value: 35.0
	Estimation Comments	The estimate of the relative bioavailability (%) is adjusted for the period effects in the ANOVA. The standard deviation is actually the gCV. CIs are based on the residual error from ANOVA, considering only the data from the 2 compared treatments.

Adverse Events

Time Frame	Adverse events (AE) occurring up to 2 days (48 h) after single intake of Deleobuvir tablets were assigned to the respective treatment period.
Adverse Event Reporting Description	The volunteers were required to report spontaneously any AEs (and time of onset, duration, intensity). In addition, each volunteer was assessed regularly by the medical staff throughout the clinical trial (including prior to discharge from the trial centre) as well as at the end of observation and whenever necessary as deemed by the investigator.
Arm/Group Title	Deleobuvir Trial Formulation II		Deleobuvir Final Formulation		Deleobuvir Final Formulation Modified		Deleobuvir (Total)
Arm/Group Description	Trial formulation II film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.		Final formulation film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.		Final formulation modified film-coated tablets. 600 mg Deleobuvir (3 tablets à 200 mg). Oral administration with 240 mL water directly after a standard normal breakfast.		All subjects while on treatment with Deleobuvir, i.e. there is no distinction between the 3 formulations.
All Cause Mortality
	Deleobuvir Trial Formulation II		Deleobuvir Final Formulation		Deleobuvir Final Formulation Modified		Deleobuvir (Total)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Deleobuvir Trial Formulation II		Deleobuvir Final Formulation		Deleobuvir Final Formulation Modified		Deleobuvir (Total)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/17 (0%)		0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Deleobuvir Trial Formulation II		Deleobuvir Final Formulation		Deleobuvir Final Formulation Modified		Deleobuvir (Total)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/16 (25%)		4/17 (23.5%)		3/18 (16.7%)		7/18 (38.9%)
Gastrointestinal disorders
Nausea	1/16 (6.3%)		1/17 (5.9%)		1/18 (5.6%)		1/18 (5.6%)
Vomiting	1/16 (6.3%)		0/17 (0%)		0/18 (0%)		1/18 (5.6%)
General disorders
Fatigue	1/16 (6.3%)		0/17 (0%)		0/18 (0%)		1/18 (5.6%)
Nervous system disorders
Headache	3/16 (18.8%)		4/17 (23.5%)		2/18 (11.1%)		5/18 (27.8%)
Dizziness	1/16 (6.3%)		0/17 (0%)		0/18 (0%)		1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/16 (0%)		0/17 (0%)		1/18 (5.6%)		1/18 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.