A randomised double-blind placebo-controlled clinical study investigating the effects of semaglutide s.c. once-weekly versus placebo on central and peripheral inflammation in participants with Alzheimer’s disease

INTERVENTION: Product Name: ipatasertib 100mg Product Code: RO5532961 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: ipatasertib Current Sponsor code: RO5532961 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: ipatasertib 200mg Product Code: RO5532961 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: ipatasertib Current Sponsor code: RO5532961 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Zytiga Pharmaceutical Form: Tablet INN or Proposed INN: Abiraterone acetate CAS Number: 154229‐18‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: Zytiga Pharmaceutical Form: Tablet INN or Proposed INN: Abiraterone acetate CAS Number: 154229‐18‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ Trade Name: Zytiga Pharmaceutical Form: Tablet INN or Proposed INN: Abiraterone acetate CAS Number: 154229‐18‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ CONDITION: Metastatic Castrate‐Resistant Prostate Cancer ; MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration‐resistant prostate cancer System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: • To evaluate To evaluate the efficacy in the intent to treat (ITT) population; • To evaluate the efficacy in patients with PTEN‐loss tumors by immunohistochemistry (IHC); Primary end point(s): 1) Investigator‐assessed radiographic progression‐free survival (rPFS), per PCWG3 criteria Secondary Objective: • To evaluate the clinical benefit in the ITT population, and in patients with PTEN‐loss tumors by IHC; • To evaluate the efficacy in patients with Phosphatase and tensin homolog (PTEN)‐loss tumors by next‐generation sequencing; • To evaluate the safety in the ITT population and in patients with PTEN‐loss tumors by IHC; • To characterize ipatasertib and abiraterone pharmacokinetics; • To characterize ipatasertib exposure, abiraterone exposure in relation to efficacy and safety; Timepoint(s) of evaluation of this end point: 1. Approximately 7 years SECONDARY OUTCOME: Secondary end point(s): 1) Overall survival; 2) Time to pain progression; 3) Time to initiation of cytotoxic chemotherapy for prostate cancer; 4) Time to function deterioration per European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 physical function and role functioning; 5) Time to PSA progression, per the PCWG3 criteria; 6) Time to first opioid use; 7) Time to symptomatic skeletal events; 8) Objective response rate, per RECIST v1.1 and PCWG3 criteria in patients with measurable disease; 9) PSA response rate; 10) Investigator‐assessed rPFS per PCWG3 criteria; 11) Incidence, nature, and severity of adverse events; 12) Plasma concentration of ipatasertib and abiraterone; 13) Relationship between plasma concentration or PK parameters of ipatasertib and abiraterone, via safety and efficacy endpoints; Timepoint(s) of evaluation of this end point: 1‐11. Approximately 7 years; 12‐13. Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, and Cycle 6 Day 1; INCLUSION CRITERIA: ‐ Aged >= 18 years ‐ Eastern Cooperative Oncology Group performance status of 0 or 1 ‐ Adequate hematologic and organ function test results within 28 days before the first study treatment ‐ Life expectancy of at least 6 months ‐ Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined in the protocol ‐ For enrollment into the China extension cohort, residence in the People's Republic of China Disease‐Specific INCLUSION CRITERIA: ‐ Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small‐cell features ‐ Consent to provide a formalin‐fixed, paraffin‐embedded tissue block or a minimum of 15 freshly cut unstained tumor slides from the most recently collected, available tumor tissue accompanied by an associated pathology report ‐ A valid PTEN IHC result ‐ Metastatic disease documented prio