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.
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;
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;
Parallel
Oxandrolone
DrugOxandrolone bioabsorbable implant (subdermal insertion) Men: 400 mg oxandrolone (two 200 mg oxandrolone implants each) Women: 200 mg oxandrolone (one 200 mg oxandrolone implant)
Placebo
DrugPlacebo bioabsorbable implant (excipients; subdermal insertion) Men: 400 mg placebo (two 200 mg placebo implants each) Women: 200 mg placebo (one 200 mg placebo implant)
Proportion of participants experiencing at least one serious adverse event (SAE) over 24-week follow-up period
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.
Safety profile and tolerability
Assessment of the safety profile based on the incidence of any adverse events (AEs), AEs leading to treatment discontinuation, and AEs related to the local implant insertion reaction. AEs will be collected through spontaneous reports and/or clinical findings.
Biochemical profile
Composite of the number of participants who experience laboratory values for biochemical, metabolic, hormonal, and haemostasis profile outside the reference range and/or deemed clinically significant over the 24 weeks following randomisation. The following blood tests will be performed: Biochemical profile: haematocrit, platelet count, creatinine, serum urea, total bilirubin, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatine phosphokinase (CPK), total prostate-specific antigen (PSA).
Metabolic Profile
Composite of the number of participants who experience laboratory values for biochemical, metabolic, hormonal, and haemostasis profile outside the reference range and/or deemed clinically significant over the 24 weeks following randomisation. The following blood tests will be performed: Metabolic profile - total cholesterol, LDL, HDL, lipoprotein A.
Hormonal Profile
Composite of the number of participants who experience laboratory values for biochemical, metabolic, hormonal, and haemostasis profile outside the reference range and/or deemed clinically significant over the 24 weeks following randomisation. The following blood tests will be performed: Hormonal profile: serum concentration of total testosterone, free testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH).
Anthropometric Measurement Assessment
Measurements of weight, height, waist circumference, and hip circumference should be collected to calculate anthropometric indices related to cardiovascular risk in the development of diseases and comorbidities: Body Mass Index (BMI), Body Adiposity Index (BAI), Waist-to-Hip Ratio (WHR), and Waist-to-Height Ratio (WHR). The parameters will be collected during the physical examination at all in-person visits.
Changes in the Short Form Health Survey SF-36 Quality of Life Questionnaire
Number of participants with changes in the 36-Item Short Form Health Survey (SF-36). SF-36 is a patient-reported outcome (PRO) measure evaluating a participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. Items from 8 domains contribute to the PCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health
Changes in the General Anxiety Disorder Questionnaire (GAD-7)
The GAD-7 is a self-administered questionnaire that assesses generalized anxiety, composed of seven questions covering aspects such as excessive worry, difficulty controlling worry, irritability, muscle tension, fatigue, difficulty relaxing, and sleep problems. Each question is scored from 0 to 3, with a severity score ranging from 0 to 21. Cutoff points are ≥5 for mild anxiety, ≥10 for moderate anxiety, and ≥15 for severe anxiety.
Changes in the Patient Health Questionnaire (PHQ-9)
The PHQ-9 is a self-administered questionnaire focused on depression, consisting of nine questions addressing aspects like diminished interest, depressed mood, fatigue, sleep issues, appetite changes, low self-esteem, difficulty concentrating, slowed movements or agitation, and suicidal thoughts. Each question is scored from 0 to 3, with a severity score from 0 to 27. Severe depression is indicated by a score \>16.
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Science Valley Research Institute
Lead sponsor
Stin Pharma
Collaborator