PKB171 Against Placebo in Couples With Asthenozoospermia Who Wish to Conceive

Multicentre, randomised, double-blind, placebo-controlled, parallel-group trial in couples who both wish to procreate with each other. A couple consists of a male subject with asthenozoospermia and a fertile female subject.

The trial consisted of:

• a screening period (visits VS1, VS2 and VS3)
• up to three double-blind treatment cycles (Visits VR, VT1a, VTib, VT2 and VT3) and a double-blind post-treatment period (visit VP1, VP2 and VP3).

After the trial there was:

• an observation period until 32 days after delivery or termination of pregnancy (visit VP4).

Screening period:

At first visit (VS1) after giving informed consent, the couple undergo several examination to check eligibility. The trial staff interviewed the female subject to determine the usual length of ther menstrual cycle, i.. the mean value over the last six cycles.

The next visit (VS2) was performed between Day 1 and Day 5 of the female subject's mentrual cycle and after 2 to 5 days of abstinence of the male subject. The next visit (VS3) took place 12 to 15 days after VS2, and a second semen analysis will be performed.

First treatment cycle:

The next visit (VR) was performed between Day 1 and Day 5 of the female subject's next menstrual cycle. After eligibility has been confirmed, the couple was randomised to Gel PKB171 150 mg, gel PKB171 200 mg or placebo. Trial staff dispensed four units (one reserve) of IMP, ovulation test strips and subjects diary and explained their use to the couple.

Ovulation testing started 16 days before the usual end of the menstrual cycle. Therefore ovulation tests started between Day 5 and Day 19.The female was instructed to perform two ovulation tests (LH distick) each day, preferable at the same time of the day.

Within 72 hours after positive ovulation test, the couple should have three times intercourse, at intervals of 24 hours. IMP was applied after each intercourse.

Within 24 hours after second IMP, the couple attended visit VT1 for safety assessments.

The next visit (VT1B) was performed 18-20 days after positive ovulation tests of between Day 1 and Day 5 of the next menstrual cycle whatever came first.

Second treatment cycle:

If the female subject was not pregnant at VT1b trial staff dispensed IMP, ovulation test strips and subject diary for the second treatment cycle. Ovulation testing and sexual intercourse, incluidng IMP use, after positive ovulation test was repeated as in the first treatment cycle.

Visit VT2 was performed 18-20 days after positive ovulation tests of between Day 1 and Day 5 of the next menstrual cycle whatever came first.

Third treatment cycle:

If the female subject was not pregnant at VT2 trial staff dispensed IMP, ovulation test strips and subject diary for the third treatment cycle. Ovulation testing and sexual intercourse, incluidng IMP use, after positive ovulation test was repeated as in the first and second treatment cycle.

Visit VT3 was performed 18-20 days after positive ovulation tests of between Day 1 and Day 5 of the next menstrual cycle whatever came first.

Double-blind post-treatment period:

In case pregnancy was detected in the course of the trial, the next visit (VP1) was taken place 56-60 days after positive pregnancy test and fetal heart activities was examined by transvaginal ultrasound. A pregnant female subject came to visit VP2 between 8th and 16th+6 week of gestation and undergone combined first trimestre screening. The results were discussed at the next visit (VP3) which was performed up to 10 days later.

Observational period:

Within 28-32 days after delivery or termination of pregnancy. VP4 was performed, and pregnancy outcome and offspring characteristics were recorded. VP4 was performed as a telephone visit.