Randomized, Multicenter, Double-blind, Parallel, Placebo-controlled Study to Investigate the Safety and Exploratory Efficacy of the Oxandrolone Subdermal Bioabsorbable Implant as an Adjuvant Treatment in Rehabilitation Following Anterior Cruciate Ligament (ACL) Surgical Reconstruction (IMOX Study)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 96
- 试验地点
- 6
- 主要终点
- Proportion of participants experiencing at least one serious adverse event (SAE) over 24-week follow-up period
研究概览
简要总结
Rehabilitation of knee stability and function after anterior cruciate ligament (ACL) reconstruction is slow and costly. The use of anabolic steroids, such as oxandrolone, may aid in the recovery of muscle mass and strength, as well as functional capacity. Oxandrolone, derived from dihydrotestosterone, has high anabolic activity and low androgenic activity (a 13:1 ratio), making it more effective in promoting weight gain with fewer side effects compared to other steroids. Registered by the FDA and previously by ANVISA, the National Health Surveillance Agency in Brazil, it is indicated for cases of post-trauma or post-surgery weight loss. The subdermal use of oxandrolone implants is proposed to release the drug directly into the bloodstream, improving efficacy and reducing issues related to oral administration. This study evaluates the safety and tolerability of the oxandrolone subdermal bioabsorbable implant for 24 weeks versus placebo implant in both men and women as an adjuvant treatment during rehabilitation following anterior cruciate ligament (ACL) surgical reconstruction. The serum and pharmacokinetic profile of the oxandrolone subdermal bioabsorbable implant will be monitored.
详细描述
This is an exploratory phase II, randomized, double-blind, placebo-controlled, multicenter clinical study designed to evaluate the safety and tolerability profile of the oxandrolone subdermal bioabdorbable implant as an adjuvant treatment in rehabilitation following anterior cruciate ligament (ACL) reconstruction surgery.
The primary safety outcome will be the proportion of participants experiencing at least one serious adverse event (SAE) over 24-week follow-up period, collected through spontaneous reports and/or clinical findings. The primary endpoint was chosen to determine the occurrence of unacceptable, severe, and clinically significant toxicity of the experimental treatment.
The delivery profile of the subdermal bioabsorbable implant will be assessed in the by the quantification of oxandrolone over 24-week follow-up period, using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Serum samples will be collected in a subgroup of participants to analyse the pharmacokinetics (Subgroup PK, N = 20 participants).
The effectiveness of the oxandrolone subdermal bioabsorbable implant in the rehabilitation of patients after surgical ACL reconstruction will be evaluated in an exploratory manner, based on their effects on the recovery of muscle mass, muscle strength, and functional capacity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For male and female participants:
- •Ability to confirm voluntary participation and approve the Informed Consent Form;
- •Men and women aged 18 to 60 years (inclusive);
- •Body weight between 50-120 kg for men and 40-90 kg for women;
- •BMI ≤34.9 kg/m²;
- •Complete ACL rupture visualized by pre-operative magnetic resonance imaging (MRI);
- •Having undergone arthroscopic knee surgery for anterior cruciate ligament (ACL) coverage using an autologous hamstring tendon graft;
- •Presenting with an isolated ACL injury or combined with ligamentous, meniscal, or cartilage lesions visualized by MRI, provided they do not interfere with the rehabilitation protocol.
- •Classification as very active, active, or irregularly active type A according to the International Physical Activity Questionnaire (IPAQ), based on pre-ACL injury physical activity;
- •Inclusion criteria assessed at the Randomization Visit (VR/V2):
- •Continue to meet all inclusion criteria verified during the Selection Visit (VS/V1)
- •Adherence to the rehabilitation protocol, having initiated postoperative physiotherapy treatment;
- •Functional range of motion from 0 to 120º and ability to ambulate without crutches;
- •Blood pressure in the seated position in the doctor's office <180/95 mmHg;
- •Hematocrit ≤ 50%;
- •ALT less than three times the upper limit of normal;
- •Serum creatinine <2 mg/dL;
- •Total bilirubin < 3.0 mg/dL;
- •Albumin ≥ 3.5 g/dL;
- •For male participants only:
- •- Total PSA ≤ 4.1 ng/mL.
排除标准
- •For female participants only:
- •Confirmed or suspected pregnancy;
- •History of childbirth, abortion, or lactation in the last 3 months;
- •Refusal to use permitted contraceptive methods during the study and for 90 days after the end of participation in the study, unless surgically sterile or expressly declaring themselves exempt from the risk of pregnancy due to not engaging in sexual activity or engaging in non-reproductive activity;
- •Clinical signs of hyperandrogenization characterized by: hirsutism defined by a Ferriman-Gallwey score ≥ 8; or alopecia defined by hair loss of at least 50% of the participant's normal hair, which is not obvious from a distance but is only noticeable upon closer inspection; a different haircut may be necessary to cover the hair loss, but does not necessarily require a wig or hairpiece to camouflage it; or Grade 5 acne defined by a predominance of inflammatory acne lesions in the facial area;
- •Polycystic Ovary Syndrome;
- •Known or suspected breast carcinoma;
- •For male participants only:
- •- Known or suspected carcinoma of the prostate or male breast;
- •For male and female participants:
- •Previous serious injury or history of surgery on the lower limbs;
- •Knee injury more than 36 months ago;
- •Meniscal tear requiring repair or suturing during ACL reconstruction surgery that interferes with postoperative rehabilitation (e.g., immobilization or limitation of range of motion);
- •Use of patellar, quadriceps, or other hamstring tendon grafts during ACL reconstruction;
- •Known contraindication to hormone use;
- •Any condition that worsens under hormone treatment;
- •Personal history of deep vein thrombosis (DVT);
- •Known coagulopathy;
- •Known chromosomal disorders;
- •Hypersensitivity to anabolic androgenic steroids;
- •Previous treatment failure with Oxandrolone;
- •Concomitant use of testosterone (or analogues) and other anabolic androgenic steroids, or prior use without completion of an adequate washout period before baseline serum testosterone sampling for study eligibility determination and randomization, in any pharmaceutical formulation within the last 3 months. Practical clinical washout will be based on recovery of baseline serum testosterone levels to <300 ng/dL. The minimum recommended washout periods are 2-3 days for transdermal gel formulations, 3 weeks for short-acting testosterone esters (enanthate or cypionate; intramuscular or subcutaneous), and 8 weeks for long-acting testosterone esters (undecanoate; intramuscular).
- •Pituitary tumor;
- •Creatinine levels >2 mg/dL or history of chronic kidney disease;
- •Myocardial infarction in the last 6 months;
- •Uncontrolled dyslipidemia;
- •Uncontrolled diabetes;
- •Patients with chronic obstructive pulmonary disease (COPD) unresponsive to bronchodilators;
- •Concomitant use of warfarin or another oral anticoagulant during experimental treatment.
- •Irregularly active type B or sedentary classification on the International Physical Activity Questionnaire (IPAQ), based on pre-ACL injury physical activity;
- •Athlete engaged in paid physical activity;
- •Known psychiatric diagnosis, including disorder Major or persistent depressive disorder, bipolar disorder, anxiety, social phobia, specific phobias or obsessive-compulsive disorder, psychotic disorder, personality disorder, eating disorder, neurocognitive disorders, and developmental or somatoform disorders (somatization or hypochondria);
- •Presence of voiding disorder;
- •Known diagnosis of fibromyalgia;
- •Participation in other clinical trial protocols in the last 30 days;
- •Participant who, in the investigator's opinion, presents other conditions or clinical or laboratory alterations that make them ineligible to participate in the study;
- •Exclusion criteria assessed at the Randomization Visit (VR/V2):
- •The participant came to meet any exclusion criterion verified at the Selection Visit (SV/V1);
- •Presenting postoperative complications such as stiffness and/or healing in the knee requiring additional procedures.
研究组 & 干预措施
Oxandrolone
Absorbable oxandrolone implant (subdermal insertion) Men: 400 mg oxandrolone (two 200 mg oxandrolone implants each) Women: 200 mg oxandrolone (one 200 mg oxandrolone implant)
干预措施: Oxandrolone (Drug)
Placebo
Absorbable placebo implant (excipients; subdermal insertion) Men: 400 mg placebo (two 200 mg placebo implants each) Women: 200 mg placebo (one 200 mg placebo implant)
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of participants experiencing at least one serious adverse event (SAE) over 24-week follow-up period
时间窗: From randomization to the end of study on Week 24.
The adverse events will be collected through spontaneous reports and/or clinical findings. The primary endpoint was chosen to determine the occurrence of unacceptable, severe, and clinically significant toxicity of the experimental treatment.
Combination of serious adverse events (SAEs) related to treatment accumulated within 24 weeks of oxandrolone or placebo pellet insertion and collected through spontaneous reporting and/or clinical findings
时间窗: From randomization to the end of study on Week 24.
The primary safety outcome is a composite of serious adverse events (SAEs) related to treatment accumulated over 24 weeks following oxandrolone or placebo implant insertion, collected from the time of informed consent signature through spontaneous reports and clinical findings.
次要结局
- Safety profile and tolerability(From randomization to the end of study on Week 24.)
- Total serum oxandrolone concentration(Pre-insertion of the bioabsorbable oxandrolone implant and at 24 hours and 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks after implant insertion.)
- Area under the curve (AUC)(Pre-insertion of the bioabsorbable oxandrolone implant and at 24 hours and 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks after oxandrolone implant insertion.)
- Maximum concentration (Cmax)(Pre-insertion of the bioabsorbable oxandrolone implant and at 24 hours and 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks after oxandrolone implant insertion.)
- Time to reach maximum concentration (tmax)(Pre-insertion of the bioabsorbable oxandrolone implant and at 24 hours and 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks after oxandrolone implant insertion.)
- Half Life (t1/2)(Pre-insertion of the bioabsorbable oxandrolone implant and at 24 hours and 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks after oxandrolone implant insertion.)
- Metabolic Profile(At pre-insertion, 4, 12, and 24 weeks after randomization)
- Hormonal Profile(At pre-insertion, 4, 12, and 24 weeks after randomization)
- Hemostasis Parameters(At pre-insertion, 4, 12, and 24 weeks after randomization)
- Total serum oxandrolone concentration(Pre-insertion of the oxandrolone implant; various times after the insertion of the oxandrolone implant and 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.)
- Maximum concentration (Cmax)(Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.)
- Time to reach maximum concentration (tmax)(Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.)
- Half Life (t1/2)(Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.)
- Participants who experience androgenization(At pre-insertion and 4, 12 and 24 weeks after randomization)
- Biochemical profile(At pre-insertion, 4, 12, and 24 weeks after randomization)
- Area under the curve (AUC)(Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.)