A Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of a Post-coital Intravaginal Gel of PKB171 in Couples With Mild Male Factor Infertility.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 732
- 试验地点
- 12
研究概览
简要总结
The test medication Gel PKB171 is a vaginal gel that has not yet been licensed by the regulatory authorities. However, the active substance pentoxifylline has been available as tablets for decades and is used to increase peripheral blood flow in patients with circulation problems. Additionally, pentoxifylline is used to treat sperm samples in artificial insemination and test tube fertilisation to increase the mobility of sperm.
A phase I clinical trial, 30 women were treated with Gel PKB171 for up to three times. Gel PKB171 was generally well tolerated and the most common side effects were local reactions like vaginal discharge and itching.
A phase II clinical trial, investigate the efficacy and safety of two concentrations of PKB171 versus placebo in couples with asthenozoospermia who wish to conceive. A total of 72 couples were planned to be included in the study. Finally, 28 couples were enrolled, and 11 couples were randomised. Within this trial, two concentrations of pentoxifylline gel were compared (5 mL of gel PKB171 containing 150 mg (3%) of pentoxifiylline, and 5 mL of gel PKB171 containing and 200 mg (4%) of pentoxifylline. Both doses were tolerated well and revealed no safety concerns as assessed by AEs, local Gel PKB171 tolerability, laboratory parameters, vital signs, gynaecologic and physical examination, or transvaginal ultrasound findings. This study was prematurely discontinued due to low numbers of eligible subjects and high recruitment failure rates, despite several protocol amendments. PKB171 gel was well tolerated and revealed no safety concerns as assessed by AEDTs, local IMP tolerability, analytical parameters, vital signs, physical and gynecological examination, or transvaginal ultrasound findings.
The aim of this clinical trial is to assess the safety and efficacy of the gel PKB171 compared to a placebo gel in couples with mild male factor infertility, unable to conceive in the last 6 and 24 months.
Additionally, the safety and local tolerability of Gel PKB171 will be further investigated.
详细描述
Phase II/III multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of a post-coital intravaginal gel of PKB171 in couples with mild male factor infertility.
The purpose of this study is to assess the safety and efficacy of the gel PKB171 compared to a placebo gel in couples with mild male factor infertility, unable to conceive in the last 6 and 24 months. Gel PKB171 contains pentoxifylline, which is used in assisted reproduction to treat sperm samples because of its ability to improve progressive sperm mobility and has reported to increase the pregnancy rate in couples with oligospermia and/or asthenozoospermia previous in vitro fertilization (IVF) failures.
The trial consisted of:
- A screening period
- Up to three double-blind treatment cycles.
- Follow-up of up to 6-8 weeks of gestation to check for clinical pregnancy (detectable fetal heartbeat).
- Long-term follow-up period until 4 weeks after delivery to assess gestational age at delivery (preterm, full-term, post-term delivery), fetal anomalies, incidence of obstetric complications (gestational hypertension, gestational diabetes, post-partum hemorrhage, NICU admission, maternal admission to ICU), mode of delivery, and live birth rate.
Screening period At the first visit (V1), inclusion criteria will be assessed to check eligibility. Trial staff will interview the couple and explain the study protocol. Consent form will be signed at that appointment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 38 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects eligible for inclusion in this study must meet all the following criteria:
- •Written informed consent form signed before any study test or procedure.
- •Unable to conceive for more than 6 months and less than 24 months, despite regular and adequate unprotected sexual intercourse.
- •Willing and able to comply with the protocol.
- •Female subjects with the following criteria:
- •Age ≥ 18 and ≤ 38 years.
- •Regular spontaneous menstrual cycles with a 25- to 35-day length (intercycle variation less than 5 days) within the last six cycles before the first visit.
- •Normal uterine cavity shown on transvaginal sonography.
- •Normal ovarian reserve, demonstrated by AMH ≥ 1 ng/ml at day 2-5 of the cycle.
- •Antral follicle count (sum of both ovaries) ≥ 6
- •Male subjects with the following criteria:
- •Age ≥ 18 and ≤ 50 years.
- •Spermiogram with semen volume ≥ 1mL, concentration > 11 M/mL, < 42% total mobility and normal forms ≥ 2%
排除标准
- •Subjects eligible for this study, both women and men, must not meet any of the following criteria:
- •Body mass Index (BMI) < 18 and ≥ 32 kg/m².
- •Any sexual intercourse with another partner (other than corresponding trial subject) within 12 weeks entry in the study and during it.
- •Couples who had any previous assisted reproductive technology (ART) cycle (in vitro fertilization, IVF, or intracytoplasmic sperm injection, ICSI) before inclusion into the trial.
- •Active hepatitis B, C, HIV, genital herpes, Chlamydia, Gonorrhea or Syphilis infection.
- •History of malignant disease (cancer). Previous or planned chemotherapy or radiotherapy.
- •History of cerebral or retinal hemorrhage, acute myocardial infarction.
- •In females: Prohibited concomitant intravaginal products or procedures.
- •Hypersensitivity or intolerance to pentoxifylline, xanthine derivatives or any of the excipients of the IMP.
- •Employees of the investigator or trial center, with direct involvement in the proposed trial or other studies under the direction of that investigator or trial center, as well as family members of the employees or the principal investigator.
- •People committed to an institution by virtue of an order issued either by the judicial or other authorities.
- •Reasonable expectation that the subject will not be able to satisfactorily complete the study:
- •History of current psychiatric illness that would interfere with the subject's ability to comply with protocol requirements or give informed consent.
- •History of alcohol or drug abuse that would interfere with the subject's ability to comply with protocol requirements.
- •Receipt of any investigational drug within three months of screening visit.
- •Previous enrolment in this trial.
- •Documented noncompliance.
- •Any other condition of the subject that in the opinion of the investigator may compromise evaluation of the trial treatment or may jeopardize subject's safety or compliance to protocol requirements.
- •Patients with peptic ulcers or recent history thereof.
- •Patients with haemorrhage (e.g. extensive retinal bleeding) or at risk of increased bleeding
- •Patients with severe coronary artery disease, when in the physician's judgement myocardial stimulation might prove harmful.
- •Patients with severe hepatic and renal impairment.
- •Patients without adequate laboratory parameters according to the normal ranges of local laboratory.
- •Female risk factors of infertility defined by any of the following:
- •Absence of any or both ovaries.
- •Abnormal uterine cavity assessed by transvaginal sonography. Specially, submucosal fibroids, intramural fibroids affecting the uterine cavity (any size), more than 5 intramural fibroids ≥ 4 cm in diameter, or more than 6 intramural fibroids of any size. Women with any subserosal fibroid ≥ 8cm will also be excluded.
- •Risk factors for fallopian tube obstruction as abdominal surgery, diseases such as endometriosis, tuberculosis, ruptured appendix or peritonitis, Pelvic Inflammatory Disease (PID), Chlamydia and gonorrhea.
- •Antecedents of long-term amenorrhea, polycystic ovarian syndrome, type III or IV endometriosis, or fallopian tube obstruction.
- •Previous gynecological surgery, excluding caesarean section or myomectomy within predefined limits.
- •For women, prohibited concomitant therapies within 28 days before enrolled into the study until last treatment visit: sex hormones, selective estrogen receptor modulators, aromatase inhibitors or oral pentoxifylline.
- •Two or more clinical or preclinical spontaneous miscarriages.
- •Lactation or pregnancy.
- •Known abnormal karyotype
- •Male risk factors of infertility defined by any of the following:
- •Vasectomy
- •Known genetic abnormalities related to infertility:
- •i.Endocrine or systemic disorders causing hypergonadotropic hypogonadism (either, congenital or acquired).
- •ii.Known abnormal karyotype
- •Previously diagnosed varicocele
- •The use of certain drugs (e.g., anabolic steroids, antineoplastic agents, erythromycin, tetracycline, gentamycin).
- •Viral process with fever ≥ 38ºC in the past 70 days