Trial Outcomes & Findings for Safety, Efficacy, Tolerability and Pharmacokinetics of LF111 (Drospirenone 4.0 mg) During 13 Cycles (NCT NCT02269241)

Last Updated: 2019-08-06

Results Overview

Pearl index (PI) from Evaluable Cycles in non-breastfeeding women aged ≤ 35 years (at the time of trial enrollment). The PI calculation was based on the following formula: PI(evaluable cycles)= (∑ on-drug confirmed pregnancy ∈{exposure cycles})/(#{exposure cycles} ) X 1300

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1552 participants

Primary outcome timeframe

up to 13 months

Results posted on

2019-08-06

Participant Flow

Participant milestones

Participant milestones
Measure	Drospirenone 4 mg Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Overall Study STARTED	1552
Overall Study COMPLETED	352
Overall Study NOT COMPLETED	1200

Reasons for withdrawal

Reasons for withdrawal
Measure	Drospirenone 4 mg Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Overall Study Lost to Follow-up	269
Overall Study Withdrawal by Subject	155
Overall Study Protocol Violation	1
Overall Study Physician Decision	7
Overall Study Pregnancy	15
Overall Study Wish for pregnancy	5
Overall Study Development of an exclusion criteria	16
Overall Study Adverse Event	113
Overall Study At the specific request of the sponsor	20
Overall Study Several reasons not classified	53
Overall Study Screening failures	546

Baseline Characteristics

Safety, Efficacy, Tolerability and Pharmacokinetics of LF111 (Drospirenone 4.0 mg) During 13 Cycles

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LF111 (Drospirenone 4mg) n=1006 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Age, Customized <=35 years	928 participants n=5 Participants
Age, Customized >35 years	78 participants n=5 Participants
Sex: Female, Male Female	1006 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	229 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	777 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	13 Participants n=5 Participants
Race (NIH/OMB) Asian	20 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	5 Participants n=5 Participants
Race (NIH/OMB) Black or African American	358 Participants n=5 Participants
Race (NIH/OMB) White	571 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 13 months

Population: The population includes all non-breastfeeding subjects aged ≤ 35 years who were randomized, received at least one dose of study drug with sexual activity without using back-up contraception.

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=915 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Number of Pregnancies (Evaluable Cycles)	2.9 Pearl Index Interval 1.5 to 5.1

SECONDARY outcome

Timeframe: up to 13 months

Population: The population includes all non-breastfeeding subjects aged ≤ 35 years who were randomized and received at least one dose of study drug.

Pearl Index based on overall cycles (overall PI) in women aged ≤ 35 years (at the time of trial enrollment) (confirmed pregnancies)

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=915 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Number of Pregnancies (All)	2.7 Pearl Index Interval 1.4 to 4.7

SECONDARY outcome

Timeframe: up to 13 months

Population: The population includes all non-breastfeeding subjects aged ≤ 35 years who were randomized, received at least one dose of study drug and used the IMP correctly.

PI for method failures in women aged ≤ 35 years (at the time of trial enrollment) (confirmed pregnancies)

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=915 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Number of Pregnancies (Method Failures)	3.4 Pearl Index Interval 1.4 to 7.0

SECONDARY outcome

Timeframe: up to 13 months

Population: The population includes all subjects aged ≤ 35 years who were randomized, received at least one dose of study drug with evaluable cycles.

Pregnancy ratio in women aged ≤ 35 years (at the time of trial enrollment)

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=915 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Pregnancy Ratio	2.46 Cumulative Pregnancy Rate (%) Interval 0.87 to 4.03

SECONDARY outcome

Timeframe: up to 13 months

Population: The population includes all ages subjects who were randomized and received at least one dose of study drug, non-breastfeeding women and used the IMP correctly.

Overall PI, PI for method failures, PI (using evaluable cycles) and pregnancy ratio (life table analysis) in all women and in women up to 13 months (confirmed pregnancies)

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=993 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Overall PI, PI for Method Failures	2.9 Pearl Index Interval 1.2 to 6.1

SECONDARY outcome

Timeframe: up to to 13 months

Population: The population includes all subjects who received at least one dose of the IMP.

Adverse events and changes in vital signs, clinical laboratory parameters

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=1006 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Number of Participants With Adverse Events as a Measure of Safety	667 Subjects

SECONDARY outcome

Timeframe: up to 13 months

Population: The population includes all subjects in full analysis set with bleeding.

Vaginal bleeding pattern

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=662 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Tolerability; Vaginal Bleeding Pattern	505 Subjects with bleeding

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 13 months

Population: The population includes evaluable cycles in non-breastfeeding women aged ≤ 35 years , who were randomized and received at least one dose of study drug, including confirmed and suspected, non-confirmed pregnancies.

PI for evaluable cycles in women aged ≤ 35 years in total and by BMI and weight subgroups based on confirmed and on confirmed and suspected, non-confirmed pregnancies

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=915 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Number of Pregnancies (by BMI and Weight) Pearl Index BMI<30	4.1 Pearl Index Interval 2.0 to 7.3
Number of Pregnancies (by BMI and Weight) Pearl Index BMI>=30	2.9 Pearl Index Interval 0.8 to 7.3
Number of Pregnancies (by BMI and Weight) Weight < Median	5.1 Pearl Index Interval 2.4 to 9.3
Number of Pregnancies (by BMI and Weight) Weight >= Median	2.3 Pearl Index Interval 0.8 to 5.5

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 13 months

Population: The population includes all ages subjects, non-breastfeeding women, who were randomized and received at least one dose of study drug, including confirmed and suspected, non-confirmed pregnancies.

Overall PI based on confirmed and on confirmed and suspected, non-confirmed pregnancies in total and by BMI and weight subgroups

Outcome measures

Outcome measures
Measure	Drospirenone 4 mg n=993 Participants Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Overall Pregnancies Pearl Index BMI<30	3.3 Pearl Index Interval 1.7 to 6.0
Overall Pregnancies Pearl Index BMI>=30	2.3 Pearl Index Interval 0.6 to 5.8
Overall Pregnancies Weight < Median	4.2 Pearl Index Interval 2.0 to 7.7
Overall Pregnancies Weight >= Median	1.9 Pearl Index Interval 0.6 to 4.4

Adverse Events

Drospirenone 4mg

Serious events: 17 serious events

Other events: 341 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Drospirenone 4mg n=1006 participants at risk Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Metabolism and nutrition disorders HYPERKALAEMIA	0.50% 5/1006 • 3 years
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.10% 1/1006 • 3 years
Psychiatric disorders DRUG ABUSE	0.10% 1/1006 • 3 years
Nervous system disorders INTRACRANIAL ANEURYSM	0.10% 1/1006 • 3 years
Infections and infestations APPENDICITIS	0.10% 1/1006 • 3 years
Pregnancy, puerperium and perinatal conditions ECTOPIC PREGNANCY	0.10% 1/1006 • 3 years
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.10% 1/1006 • 3 years
Injury, poisoning and procedural complications OVERDOSE	0.10% 1/1006 • 3 years
Hepatobiliary disorders BILIARY COLIC	0.10% 1/1006 • 3 years
Infections and infestations CELLULITIS	0.10% 1/1006 • 3 years
Injury, poisoning and procedural complications MULTIPLE INJURIES	0.10% 1/1006 • 3 years
Pregnancy, puerperium and perinatal conditions ABORTION SPONTANEOUS	0.10% 1/1006 • 3 years
Pregnancy, puerperium and perinatal conditions INDUCED LABOUR	0.10% 1/1006 • 3 years

Other adverse events

Other adverse events
Measure	Drospirenone 4mg n=1006 participants at risk Single treatment arm receives LF111 film-coated tablets (24 white tablets containing 4.0 mg drospirenone, 4 green placebo tablets), oral administration once daily.
Reproductive system and breast disorders Metrorrhagia	5.2% 52/1006 • 3 years
Reproductive system and breast disorders Dysmenorrhoea	4.4% 44/1006 • 3 years
Reproductive system and breast disorders Breast pain	4.3% 43/1006 • 3 years
Reproductive system and breast disorders Breast tenderness	3.0% 30/1006 • 3 years
Reproductive system and breast disorders Menorrhagia	1.7% 17/1006 • 3 years
Reproductive system and breast disorders Vaginal haemorrhage	1.2% 12/1006 • 3 years
Reproductive system and breast disorders Amenorrhoea	1.1% 11/1006 • 3 years
Reproductive system and breast disorders Menstruation irregular	0.80% 8/1006 • 3 years
Reproductive system and breast disorders Vulvovaginal dryness	0.50% 5/1006 • 3 years
Gastrointestinal disorders Nausea	4.0% 40/1006 • 3 years
Gastrointestinal disorders Abdominal pain	1.1% 11/1006 • 3 years
Gastrointestinal disorders Abdominal distension	0.80% 8/1006 • 3 years
Gastrointestinal disorders Vomiting	0.70% 7/1006 • 3 years
Nervous system disorders Headache	4.7% 47/1006 • 3 years
Nervous system disorders Migraine	0.70% 7/1006 • 3 years
Skin and subcutaneous tissue disorders Acne	3.0% 30/1006 • 3 years
Skin and subcutaneous tissue disorders Alopecia	0.60% 6/1006 • 3 years
Investigations Weight increased	2.3% 23/1006 • 3 years
Investigations Blood potassium increased	0.50% 5/1006 • 3 years
Psychiatric disorders Libido decreased	1.1% 11/1006 • 3 years
Psychiatric disorders Mood swings	0.99% 10/1006 • 3 years
Psychiatric disorders Depression	0.70% 7/1006 • 3 years
Psychiatric disorders Affect lability	0.60% 6/1006 • 3 years
Psychiatric disorders Irritability	0.50% 5/1006 • 3 years
Infections and infestations Vulvovaginal mycotic infection	0.80% 8/1006 • 3 years
Infections and infestations Fungal infection	0.50% 5/1006 • 3 years
Infections and infestations Vulvovaginal candidiasis	0.50% 5/1006 • 3 years
Metabolism and nutrition disorders Decreased appetite	0.60% 6/1006 • 3 years
Vascular disorders Hot flush	0.50% 5/1006 • 3 years

Additional Information

Dr. Enrico Colli, Chief Scientific Officer

Exeltis

Phone: +34917711500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place