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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
96
Oxandrolone bioabsorbable implant (subdermal insertion) Men: 400 mg oxandrolone (two 200 mg oxandrolone implants each) Women: 200 mg oxandrolone (one 200 mg oxandrolone implant)
Placebo bioabsorbable implant (excipients; subdermal insertion) Men: 400 mg placebo (two 200 mg placebo implants each) Women: 200 mg placebo (one 200 mg placebo implant)
Unimed Fortaleza
Fortaleza, Ceará, Brazil
RECRUITINGFaculdade Ciências Médicas de Minas Gerais (CMMG)
Belo Horizonte, Minas Gerais, Brazil
RECRUITINGCentro de Oncologia do Paraná
Curitiba, Paraná, Brazil
RECRUITINGUnimed Brusque
Brusque, Santa Catarina, Brazil
RECRUITINGHospital e Maternidade Christóvão da Gama
Santo André, São Paulo, Brazil
RECRUITINGSanta Casa de Santos
Santos, São Paulo, Brazil
RECRUITINGProportion 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.
Time frame: From randomization to the end of study on Week 24.
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.
Time frame: From randomization to the end of study on Week 24.
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).
Time frame: At pre-insertion, 4, 12, and 24 weeks after randomization
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.
Time frame: At pre-insertion, 4, 12, and 24 weeks after randomization
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).
Time frame: At pre-insertion, 4, 12, and 24 weeks after randomization
Hemostasis Parameters
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: Haemostasis parameters - D-dimer, SHBG, and free S-protein.
Time frame: At pre-insertion, 4, 12, and 24 weeks after randomization
Total serum oxandrolone concentration
In a subgroup of 20 participants from selected centers, serum oxandrolone concentrations will be assessed to determine the oxandrolone concentration. Serum samples will be processed and stored for analysis by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) in a central laboratory.
Time frame: 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)
The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS)
Time frame: 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)
The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS)
Time frame: 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)
The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS)
Time frame: 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)
The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS)
Time frame: 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.
Participants who experience androgenization
The appearance and worsening of signs of androgenization in female participants will be monitored at all clinical visits throughout the study. A physician or other qualified professional will assess hirsutism, alopecia, and acne, and the assessment of voice deepening will be performed by the participant´s self-report.
Time frame: At pre-insertion and 4, 12 and 24 weeks after randomization
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