Effect of BI 207127 + Faldaprevir on Blood Levels of Oral Contraceptives Containing Ethinylestradiol and Levonorgestrel

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01941615
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 2
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

Investigate the effect of multiple oral doses of BI 207127 + faldaprevir (FDV) on the multiple dose pharmacokinetics of ethinylestradiol and levonorgestrel (Microgynon®) in healthy premenopausal female volunteers.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Two-period, Fixed-sequence, Phase I Trial to Evaluate the Effect of Multiple Doses of BI 207127 + Faldaprevir on the Multiple-dose Pharmacokinetics of a Combination of Ethinylestradiol and Levonorgestrel in Healthy Premenopausal Female Subjects
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 207127 + faldaprevir + Microgynon Period A: Microgynon®; Period B: Microgynon® + FDV + BI 207127	Drug: faldaprevir; oral doses for 10 days (period B); Drug: Microgynon®; oral doses for 23 days (period A+B); Drug: BI 207127; oral doses for 10 days (period B)

Outcome Measures

Primary Outcome Measures

1. AUCtau,ss of Ethinylestradiol [Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives]

   Area under the concentration-time curve of ethinylestradiol in plasma at steady state over a uniform dosing interval t (AUCtau,ss).

2. Cmax,ss of Ethinylestradiol [Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives]

   Maximum measured concentration of ethinylestradiol in plasma at steady state over a uniform dosing interval t

3. C24,ss of Ethinylestradiol [Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives]

   Measured concentration of ethinylestradiol in plasma at steady state 24 hours after drug administration.

4. AUCtau,ss of Levonogestrel [Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives]

   Area under the concentration-time curve of levonogestrel in plasma at steady state over a uniform dosing interval t.

5. Cmax,ss of Levonogestrel [Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives]

   Maximum measured concentration of levonogestrel in plasma at steady state over a uniform dosing interval t.

6. C24,ss of Levonogestrel [Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives]

   Measured concentration of levonogestrel in plasma at steady state 24 hours after drug administration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• Healthy female subjects

• Age 18 to 35 years (inclusive)

• Body Mass Index 20-29.9 kg/m2

• Use of hormonal contraception (i.e. oral contraceptives, hormonal contraceptive vaginal ring, but not hormone-containing intrauterine devices, depot injections or contraceptive implants)

Exclusion criteria:

• Any relevant deviation from healthy conditions

• Subject is assessed by the investigator as unsuitable for inclusion, 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

• Positive pregnancy test, pregnancy or planning to become pregnant within 1 month of study completion, or lactation

• Any relevant finding of the gynaecological examination

• Thrombotic predisposition according to thrombophilic testing

• Existing or history of arterial thrombotic or embolic processes, conditions which predispose to them e.g. disorders of the clotting processes, valvular heart disease and atrial fibrillation

• Existing or history of confirmed venous thromboembolism, family history of venous thromboembolism, and other known risk factors for venous thromboembolism.

• Relevant varicosis

• No use of an additional contraceptive method from screening examination until 1 month after last study drug administration (acceptable methods are considered to be barrier methods, sexual abstinence, non-hormone-containing intrauterine device, or vasectomisation for the male partner).

Use of hormone-containing intrauterine device, depot injection or contraceptive implants

• Any history of relevant liver diseases (e.g. disturbances of liver function, jaundice or persistent itching during a previous pregnancy, Dubin-Johnson syndrome, Rotor syndrome, or previous or existing liver tumours)

• AST (aspartate transaminase) and/or ALT (alanine transaminase) > 1.5 ULN (upper limit of normal)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1241.31.2 Boehringer Ingelheim Investigational Site	Mannheim		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: NCT01941615
• Other Study ID Numbers: 1241.31; 2013-000298-62
• First Posted: Sep 13, 2013
• Last Update Posted: Apr 11, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Ethinyl estradiol, levonorgestrel drug combination; Ethinyl Estradiol-Norgestrel Combination

Study Results

Participant Flow

Recruitment Details	This trial was planned to include 18 healthy premenopausal female subjects. Because this trial was prematurely discontinued during the run-in period, only 16 subjects were entered.

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Period Title: Run in Treatment: Microgynon®
STARTED	16
COMPLETED	16
NOT COMPLETED	0
Period Title: Run in Treatment: Microgynon®
STARTED	0
COMPLETED	0
NOT COMPLETED	0
Period Title: Run in Treatment: Microgynon®
STARTED	0
COMPLETED	0
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.5 (3.7)
Sex: Female, Male (Count of Participants)
Female	16 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	AUCtau,ss of Ethinylestradiol
Description	Area under the concentration-time curve of ethinylestradiol in plasma at steady state over a uniform dosing interval t (AUCtau,ss).
Time Frame	Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives

Outcome Measure Data

Analysis Population Description

Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Measure Participants	0

2. Primary Outcome

Title	Cmax,ss of Ethinylestradiol
Description	Maximum measured concentration of ethinylestradiol in plasma at steady state over a uniform dosing interval t
Time Frame	Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives

Outcome Measure Data

Analysis Population Description

Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Measure Participants	0

3. Primary Outcome

Title	C24,ss of Ethinylestradiol
Description	Measured concentration of ethinylestradiol in plasma at steady state 24 hours after drug administration.
Time Frame	Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives

Outcome Measure Data

Analysis Population Description

Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Measure Participants	0

4. Primary Outcome

Title	AUCtau,ss of Levonogestrel
Description	Area under the concentration-time curve of levonogestrel in plasma at steady state over a uniform dosing interval t.
Time Frame	Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives

Outcome Measure Data

Analysis Population Description

Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Measure Participants	0

5. Primary Outcome

Title	Cmax,ss of Levonogestrel
Description	Maximum measured concentration of levonogestrel in plasma at steady state over a uniform dosing interval t.
Time Frame	Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives

Outcome Measure Data

Analysis Population Description

Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Measure Participants	0

6. Primary Outcome

Title	C24,ss of Levonogestrel
Description	Measured concentration of levonogestrel in plasma at steady state 24 hours after drug administration.
Time Frame	Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives

Outcome Measure Data

Analysis Population Description

Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.

Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days.
Measure Participants	0

Adverse Events

Time Frame	until end of run-in period up to 49 days
Adverse Event Reporting Description	study was terminated after run-in period
Arm/Group Title	Deleobuvir + Faldaprevir + Microgynon
Arm/Group Description	In the run-in period starting between Day -56 and Day -28, all subjects were to take 1 Microgynon® tablet (combined oral contraceptive ethinylestradiol / levonorgestrel) once daily for 21 to 49 days (depending on the menstrual cycle) until Day -8. In the last 7 days of the run-in period (Day -7 to Day -1), no treatment was given in order to induce withdrawal bleeding. The next day was to be Day 1 of the study. Subjects who were using oral contraceptives before the study started the run-in period after the usual tablet-free interval of 7 days. Subjects who were using hormonal contraceptive vaginal rings before the study started the run-in-period after the usual hormone-free interval of 7 days.
All Cause Mortality
	Deleobuvir + Faldaprevir + Microgynon
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Deleobuvir + Faldaprevir + Microgynon
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Deleobuvir + Faldaprevir + Microgynon
	Affected / at Risk (%)	# Events
Total	4/16 (25%)
Infections and infestations
Nasopharyngitis	1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/16 (6.3%)
Nervous system disorders
Headache	1/16 (6.3%)
Reproductive system and breast disorders
Breast pain	1/16 (6.3%)
Metrorrhagia	2/16 (12.5%)
Uterine pain	1/16 (6.3%)

Limitations/Caveats

This trial was prematurely discontinued during the run-in period. During the run-in period, subjects were to receive Microgynon® once daily for 21 to 49 days. The investigational products Deleobuvir + faldaprevir were not administered.

More Information

Certain Agreements

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

Other - 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.