Change From Period Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index.
Time frame: At baseline and at 3 and 6 Months each treatment period.
Sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI), a self-reported instrument with a global score from 0 to 21. Higher scores indicate worse sleep quality.
Change From Period Baseline in Health-Related Quality of Life on the 36-Item Short Form Survey.
Time frame: At baseline and at Months 3 and 6 of each treatment period.
Health-related quality of life will be assessed using the Medical Outcomes Study 36-Item Short Form Survey (SF-36). Scores are calculated for 8 domains from 0 to 100; higher scores indicate better health-related quality of life.
Change From Period Baseline in Pain-Related Quality of Life on the WHOQOL-Pain Instrument.
Time frame: At baseline and at Months 3 and 6 of each treatment period.
Pain-related quality of life will be assessed using the Portuguese version of the WHOQOL-Pain instrument. Scoring and interpretation will follow the validated instrument manual.
Change From Period Baseline in Fibromyalgia Impact Questionnaire Score Among Participants With Fibromyalgia.
Time frame: At baseline and at Months 3 and 6 of each treatment period.
Functional impact among participants with a clinical diagnosis of fibromyalgia will be assessed using the Fibromyalgia Impact Questionnaire (FIQ). The scale will be scored according to the validated Portuguese version; higher scores indicate greater disease impact.
Change From Baseline in Bone Mineral Density Measured by Dual-Energy X-Ray Absorptiometry.
Time frame: At baseline and at the final study visit, approximately 12 months after enrollment.
Bone mineral density and body composition will be assessed using dual-energy X-ray absorptiometry (DXA). Bone mineral density will be reported in grams per square centimeter and interpreted using T-scores according to applicable clinical criteria.
Change From Period Baseline in Serum Bone Turnover Biomarkers.
Time frame: At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
Serum bone health biomarkers will include the final protocol-specified panel of alkaline phosphatase, total and ionized calcium, 25-hydroxyvitamin D, and parathyroid hormone. If procollagen type 1 N-terminal propeptide and C-terminal telopeptide are retained in the final protocol, they should be listed here explicitly.
Association of CB2 and TRPV1 Genetic Variants With Pain Treatment Response.
Time frame: Genotyping at baseline; association with pain response through the end of each treatment period, approximately 12 months.
Genotyping of cannabinoid receptor 2 (CB2/CNR2) and transient receptor potential vanilloid 1 (TRPV1) variants will be performed using real-time polymerase chain reaction. Associations between genotype or haplotype and the prespecified Visual Analog Scale pain response will be evaluated.
Change From Baseline in Salivary Endocannabinoid Concentrations.
Time frame: Use the final collection schedule; do not submit this entry until the protocol is harmonized as baseline-only or serial sampling.
Salivary concentrations of anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide will be quantified by liquid chromatography-tandem mass spectrometry and reported in nanograms per milliliter.
Number of Participants With Treatment-Emergent Adverse Events.
Time frame: From first study product administration through the end of each treatment period, approximately 6 months per period.
Adverse events will be collected through clinical visits and weekly remote pharmacotherapeutic monitoring. Events will be classified by severity, seriousness, relatedness to study treatment, and treatment period.
Change From Period Baseline in Hepatic and Renal Safety Laboratory Values.
Time frame: At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
Safety laboratory assessments will include protocol-specified hepatic and renal tests, including aspartate aminotransferase, alanine aminotransferase, urea, and creatinine. Results will be reported in standard laboratory units.