AZD8965 for Healthy Subjects

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AstraZeneca

Must not be taking: Hormonal contraceptives

Disqualifiers: Diabetes, Hypertension, Cardiovascular, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of AZD8965 via single and multiple ascending doses in healthy participants (including Japanese and Chinese participants), and to assess the effect of food on the safety, tolerability, and PK of orally administered AZD8965.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be healthy without any ongoing medical conditions or medications that could interfere with the study.

What safety data exists for AZD8965 in healthy subjects?

There is no specific safety data available for AZD8965 in the provided research articles. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for healthy individuals, including those of Japanese and Chinese descent. It's designed to test the safety and how the body processes a new drug called AZD8965, both on an empty stomach and with food.

Inclusion Criteria

I am not breastfeeding and agree to use effective birth control if I'm sexually active.

I am a woman who cannot become pregnant, confirmed by a doctor.

I am a man who can father children and will use birth control as required.

Exclusion Criteria

I have a history of high blood pressure or heart disease.

I have a long-term infection or am at high risk for infections.

I do not have chronic conditions that affect drug metabolism.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Single Ascending Dose (SAD)

Participants receive a single dose of AZD8965 or placebo to assess safety, tolerability, and pharmacokinetics

1 week

Residential stay from Day -1 to at least 72 hours post-dose

Multiple Ascending Dose (MAD)

Participants receive multiple doses of AZD8965 or placebo to assess safety, tolerability, and pharmacokinetics

2 weeks

Residential stay from Day -1 to at least 48-72 hours post last dose

Food Effect

Participants receive AZD8965 under fasted and fed conditions to assess the effect of food on pharmacokinetics

1 week

Residential stay from Day -1 to at least 72 hours post-dose

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AZD8965 (Other)

Trial Overview The study involves giving participants either AZD8965 or a placebo (a substance with no active drug). They'll receive varying doses to see how well they tolerate it and how their bodies handle the drug over time.

Participant Groups

Group I: Part 4: Food Effect Cohort - AZD8965 Experimental Treatment 1 Intervention

Participants will receive 2 single dose treatments of AZD8965 \[following an overnight fast of at least 10 hours in a fasted state or a fed state (after a high fat meal)\].

Group II: Part 3B: Single and multiple ascending dose (SMAD) Cohort 1 (Japanese) - AZD8965 (Dose 1) Experimental Treatment 2 Interventions

Japanese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1, followed by multiple doses of AZD8965 or matching placebo from Day 3 until Day 9.

Group III: Part 3B: SMAD Cohort 2 (Chinese) - AZD8965 (Dose 1) Experimental Treatment 2 Interventions

Chinese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1, followed by multiple doses of AZD8965 or matching placebo from Day 3 until Day 9.

Group IV: Part 3A: SAD Cohort 3 (Chinese) - AZD8965 (Dose 1) Experimental Treatment 2 Interventions

Chinese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.

Group V: Part 3A: SAD Cohort 2 (Japanese) - AZD8965 (Dose 2) Experimental Treatment 2 Interventions

Japanese participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1.

Group VI: Part 3A: SAD Cohort 1 (Japanese) - AZD8965 (Dose 1) Experimental Treatment 2 Interventions

Japanese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.

Group VII: Part 2: MAD Cohort 3 - AZD8965 (Dose 3) Experimental Treatment 2 Interventions

Participants will receive multiple doses of AZD8965 (Dose 3) or matching placebo to AZD8965 from Day 1 to Day 8.

Group VIII: Part 2: MAD Cohort 2 - AZD8965 (Dose 2) Experimental Treatment 2 Interventions

Participants will receive multiple doses of AZD8965 (Dose 2) or matching placebo to AZD8965 from Day 1 to Day 8.

Group IX: Part 2: MAD Cohort 1 - AZD8965 (Dose 1) Experimental Treatment 2 Interventions

Participants will receive multiple doses of AZD8965 (Dose 1) or matching placebo to AZD8965 from Day 1 to Day 8.

Group X: Part 1: SAD Cohort 5 - AZD8965 (Dose 5) Experimental Treatment 2 Interventions

Participants will receive a single dose of AZD8965 (Dose 5) or matching placebo to AZD8965 on Day 1.

Group XI: Part 1: SAD Cohort 4 - AZD8965 (Dose 4) Experimental Treatment 2 Interventions

Participants will receive a single dose of AZD8965 (Dose 4) or matching placebo to AZD8965 on Day 1.

Group XII: Part 1: SAD Cohort 3 - AZD8965 (Dose 3) Experimental Treatment 2 Interventions

Participants will receive a single dose of AZD8965 (Dose 3) or matching placebo to AZD8965 on Day 1.

Group XIII: Part 1: SAD Cohort 2 - AZD8965 (Dose 2) Experimental Treatment 2 Interventions

Participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1.

Group XIV: Part 1: SAD Cohort 1 - AZD8965 (Dose 1) Experimental Treatment 2 Interventions

Participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Adverse drug reactions (ADRs) are harmful responses to medications that can lead to serious consequences, and they are classified into six types to help identify and manage them effectively.

Management of ADRs typically involves withdrawing the offending drug and treating the symptoms, and it is crucial to report suspected ADRs to improve drug safety and surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions: definitions, diagnosis, and management. Edwards, IR., Aronson, JK.[2022]

In a meta-analysis of 11,028 healthy participants across 394 non-oncology phase I studies, 63.7% experienced adverse events, but 85% of these were classified as mild, indicating a relatively safe profile for the study drugs.

Only 0.31% of participants experienced serious adverse events, with no deaths or life-threatening incidents reported, suggesting that while adverse events are common, they are mostly not severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying the risks of non-oncology phase I research in healthy volunteers: meta-analysis of phase I studies. Emanuel, EJ., Bedarida, G., Macci, K., et al.[2018]

In a study comparing 192 healthy volunteers in Phase I drug trials to a control group of 112 matched individuals, the Phase I participants reported significantly fewer common complaints like headaches, stomach pain, and anxiety, suggesting they may have a lower tendency to report non-drug-related adverse events.

Psychological factors, such as anxiety and depression, were found to correlate positively with the incidence of complaints, while higher self-efficacy was associated with fewer complaints, indicating that psychological characteristics can influence the reporting of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse non-drug-related complaints by healthy volunteers in Phase I studies compared to the healthy general population. Almeida, L., Coelho, R., Albino-Teixeira, A., et al.[2019]

The study analyzed 345,662 spontaneous reports of adverse drug reactions (ADRs) submitted to the German Federal Institute for Drugs and Medical Devices, revealing a steady increase in reports since 1978, primarily due to stricter legal reporting requirements.

The most commonly reported ADRs were linked to drugs for nervous system disorders, with significant differences in reporting patterns between physicians and patients, suggesting a need for better patient education on potential ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. Dubrall, D., Schmid, M., Alešik, E., et al.[2023]

The risk/benefit ratio of newly marketed drugs is often unclear due to limited premarketing studies conducted on small, homogenous populations, which may not reflect the broader, more diverse patient groups exposed to these drugs after they are approved.

Adverse drug reactions (ADRs) can range from mild to life-threatening and are common enough to have significant socioeconomic impacts, particularly in vulnerable populations such as the elderly or those with multiple health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of populations at risk and problem drugs during drug development and in pharmacotherapy. Hinderling, PH.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Adverse drug reactions: definitions, diagnosis, and management. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Quantifying the risks of non-oncology phase I research in healthy volunteers: meta-analysis of phase I studies. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

Adverse non-drug-related complaints by healthy volunteers in Phase I studies compared to the healthy general population. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Detection of populations at risk and problem drugs during drug development and in pharmacotherapy. [2019]