Clinical Trial Results:
A Pivotal, Multicenter, Non-Comparative Trial on the Contraceptive Efficacy, Safety and Tolerability of Drospirenone as LF111 During 13 Cycles
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Summary
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EudraCT number |
2010-021787-15 |
Trial protocol |
DE HU CZ RO |
Global end of trial date |
18 Feb 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Oct 2019
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First version publication date |
12 Oct 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CF111/301
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Chemo France
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Sponsor organisation address |
7 rue Victor Hugo, Sevres, France, 92310
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Public contact |
Enrico Colli, Chemo Research, 0034 91 302 15 00, enrico.colli@exeltis.com
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Scientific contact |
Enrico Colli, Chemo Research, 0034 91 302 15 00, enrico.colli@exeltis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Mar 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Feb 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To demonstrate the contraceptive efficacy of LF111
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Protection of trial subjects |
N/A
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Background therapy |
N/A | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
11 Jul 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 199
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Country: Number of subjects enrolled |
Romania: 119
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Country: Number of subjects enrolled |
Czech Republic: 178
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Country: Number of subjects enrolled |
Germany: 158
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Country: Number of subjects enrolled |
Hungary: 70
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Worldwide total number of subjects |
724
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EEA total number of subjects |
724
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
724
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 824 subjects were screened, 100 subjects were screening failures and 724 subjects were allocated to treatment (ATS). Of these 724 subjects, 11 prematurely terminated the trial before the start of treatment due to withdrawal of consent (5 subjects), ineligibility (3 subjects), other reasons (2 subjects) and pregnancy (1 subject). | ||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Healthy woman at risk of pregnancy, at the age of 18-45 y. For Germany: Woman without uncontrolled current diseases at risk of pregnancy, at the age of 18-45 y. For starters: At least 4 menstrual cycles during the last 6 m before Visit 1 were regular (i.e. cycle length between 24 and 35 days). Systolic BP<140 mmHg, diastolic BP<90 mmHg. | ||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
Blinding implementation details |
N/A
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Arms
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Arm title
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experimental | ||||||||||||||||||||||||||||||||||||
Arm description |
Single arm | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Drospirenone 4 mg film-coated tablets
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Investigational medicinal product code |
LF111
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
In this trial each subject received one tablet of IMP per day. During the medication cycle the subjects were to take 24 active tablets (each containing 4 mg DRSP) followed by four placebo tablets.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
The Safety Set (SS) consisted of all subjects who had received at least one dose of IMP
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
The Full Analysis Set (FAS) consists of all subjects who:
- are included in the SS (took at least one dose of IMP)
- who were not pregnant at the date of first IMP intake.
The full analysis set will be used for efficacy analysis.
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End points reporting groups
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Reporting group title |
experimental
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Reporting group description |
Single arm | ||
Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The Safety Set (SS) consisted of all subjects who had received at least one dose of IMP
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Full Analysis Set (FAS) consists of all subjects who:
- are included in the SS (took at least one dose of IMP)
- who were not pregnant at the date of first IMP intake.
The full analysis set will be used for efficacy analysis.
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End point title |
Overall Pearl Index [1] | ||||||
End point description |
Overall PI = number of pregnancies*1300/number of medication cycles
Overall PI was to include all pregnancies which occurred during the study. Pregnancies following premature termination of IMP were to be excluded from calculations unless intravaginal ultrasound examination and β–HCG test was not performed to determine whether the date of conception was after the premature discontinuation.
Medication cycle was defined as 28 days starting with the administration of the first tablet from the blister containing 28 tablets and ending with the last day of intake
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End point type |
Primary
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End point timeframe |
PI is calculated at the end of the study
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a single arm, open label study. Thus, a comparison to a reference product is not planned |
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| No statistical analyses for this end point | |||||||
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End point title |
Pearl Index (PI) for method failures | ||||||
End point description |
Method failure PI = number of pregnancies (M) * 1300/number of perfect medication cycles. Method failure was to include all pregnancies categorised as M. M=pregnancy where the subject was compliant with IMP dosing near the time of conception and estimated date of conception was during treatment period (extended with a maximum of 2 days).
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End point type |
Secondary
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End point timeframe |
At the end of the study
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| No statistical analyses for this end point | |||||||
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End point title |
PI after correction for additional contraception and for sexual activitis status | ||||||
End point description |
PI after correction for additional contraception and for sexual activity status = number of pregnancies (M,U) * 1300/exposure cycles excluding those with back-up contraception and without sexual activity.
M (method failure) = pregnancy where the subject was compliant with IMP dosing near the time of conception and estimated date of conception was during treatment period (extended with a maximum of 2 days).
U (user failure) = pregnancy where the subject failed to comply with IMP dosing near the time of conception and estimated date of conception was during treatment period (extended with a maximum of 2 days).
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End point type |
Secondary
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End point timeframe |
At the end of the study
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| No statistical analyses for this end point | |||||||
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End point title |
Adverse events | ||||||
End point description |
Adverse events (AEs) will be reported on a per-subject basis. This implies that even if a subject reported the same event repeatedly, the event will be counted only once. In the latter case, the event will be assigned the worst severity and strongest relationship to the IMP. The presentation of AEs is therefore restricted to the incidence per subject of AEs assigned to the Treatment or Follow-up Period.
Treatment-emergent adverse events (TEAEs) were defined as AEs which started at or after the first administration of the IMP and included those events started prior to the first administration of the IMP but which worsened after the first intake. AEs starting after the last
administration of the IMP but within the follow-up period were also regarded as treatment emergent. TEAEs leading to trial termination were obtained from the AE form, where the field “Action taken on study drug” was indicated as “drug withdrawn”.
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End point type |
Secondary
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End point timeframe |
Anytime during the study
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| No statistical analyses for this end point | |||||||
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End point title |
Clinical Laboratory Evaluation | ||||||
End point description |
Haematology: Haemoglobin, red blood cell count, mean corpuscular volume (M.C.V.) and associated parameters , haematocrit, M.C.H., white blood cell count, differential white blood cell count including neutrophils, lymphocytes, eosinophils, basophils and monocytes, platelet count
Biochemistry: Sodium, potassium, chloride, creatinine, blood urea nitrogen (BUN), calcium, glucose, total proteins, albumin, total cholesterol (HDL, LDL cholesterol), triglycerides, gamma glutamyl transferase, total and direct bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), creatine phosphokinase (CPK), lactate dehydrogenase (LDH)
Urinalysis Leukocytes, nitrite, protein, glucose, ketones, blood, pH, urobilinogen, bilirubin, haemoglobin
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End point type |
Secondary
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End point timeframe |
Blood samples for haematology, biochemistry and thyroid function assessments and urine samples for urinalysis will be collected at V1a, V3, V4, V5 (electrolytes only), and V6 (or EDV).A dipstick will be used for urinalysis at V1a, V4 and V6 (or EDV)
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| No statistical analyses for this end point | |||||||
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End point title |
vital signs | ||||||
End point description |
Body weight and body mass index, Blood pressure and heart rate
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End point type |
Secondary
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End point timeframe |
Body weight, blood pressure and heart rate were measured at screening, V4 and V6 (EDV).
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| No statistical analyses for this end point | |||||||
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End point title |
Tolerability | ||||||
End point description |
Number and rate of subjects with different bleeding patterns will be presented for each cycle or reference period. The Clopper-Pearson 95% confidence interval for rate of subjects will be calculated. Cumulative rate of subjects with different bleeding patterns for reference periods will be provided.
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End point type |
Secondary
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End point timeframe |
From Day 1 of Medication Cycle 1 (i.e. start of IMP intake) to V6/EDV, subjects will record any vaginal bleeding in their electronic diary.
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| No statistical analyses for this end point | |||||||
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End point title |
IMP acceptablitity | ||||||
End point description |
- How did you tolerate the intake of the trial medication (excellent, good, moderate, bad, no answer)
- How was your wellbeing during the intake of the trial medication (excellent, good, moderate, bad, no answer)
- Did the subject switch from another oral contraceptive to the study medication? (yes, no)
- If yes: How was your wellbeing during the intake of the trial medication in comparison to the time when you took your former oral contraceptive, for switchers from another oral contraceptive only (better, unchanged, worse, no answer)
- Acceptability of the IMP from the physician’s point of view (excellent, good, moderate, bad, no answer)
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End point type |
Secondary
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End point timeframe |
At V2 to V6/EDV, the subject will be asked by the investigator for an assessment regarding IMP acceptability
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
AEs which started at or after the first administration of the IMP and included those events started prior to the first administration of the IMP but which worsened after the first intake. AEs starting after last adm of the IMP but within the FU period.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
Safety Set
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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15 Mar 2011 |
This protocol amendment was prepared not to exclude women with a BMI > 30 kg/m2; to correct an error regarding drug accountability in the protocol; to correct the inconsistency in urinalysis laboratory parameters and to correct the inconsistency between the CRF and the protocol with respect to IMP acceptability answer options. |
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30 Jun 2011 |
With this protocol amendment the permitted delay in DRSP intake was extended from 12 to 24 hours, based on the preliminary results of the pilot study CF111/201A. Sexual activity for each medication cycle had to be confirmed in the e-diary;
Visit 6 was scheduled for Day 29+2 of the 13th medication cycle to ensure that e-diaries with complete data for the 13th medication cycle could be collected and final drug accountabilitycould be performed at Visit 6. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
