Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as No other names
AZD4041 · 3 trials · 3 indications
ETCo2 measurement is performed in the clinical pharmacology setting studies for the evaluation of respiratory function. EtCO2 is monitored and measured using a standardized methodology and configuration using MICROSREAM\^TM consumables to sample gas via nasal cannulae and the CAPNOSTREAM\^TM20P bedside monitor according to Altasciences SOP on Capnography. Using this configuration, for the spontaneously breathing healthy volunteer participant, baseline EtCO2 measurements is expected to fall within the range of 34 to 48 mmHg. An increase in EtCO2 is defined as an increase of at least 10 mmHg compared to baseline or \> 50 mmHg (sustained for at least 30 seconds). Number of participants with increased EtCO2 of at least 10 mmHg compared to baseline or \> 50 mmHg on Day 1 are reported.
ETCo2 measurement is performed in the clinical pharmacology setting studies for the evaluation of respiratory function. EtCO2 is monitored and measured using a standardized methodology and configuration using MICROSREAM\^TM consumables to sample gas via nasal cannulae and the CAPNOSTREAM\^TM20P bedside monitor according to Altasciences SOP on Capnography. Using this configuration, for the spontaneously breathing healthy volunteer participant, baseline EtCO2 measurements is expected to fall within the range of 34 to 48 mmHg. An increase in end tidal carbon dioxide (EtCO2) is defined as an increase of at least 10 mmHg compared to baseline or \> 50 mmHg (sustained for at least 30 seconds). Number of participants with increased EtCO2 of at least 10 mmHg compared to baseline or \> 50 mmHg on Day 15 are reported.
A reduction in SpO2 is defined as a reduction from baseline to \< 92% (sustained for at least 30 seconds). Number of participants with reduction in SpO2 to \< 92% on Day 1 are reported.
A reduction in SpO2 is defined as a reduction from baseline to \< 92% (sustained for at least 30 seconds). Number of participants with reduction in SpO2 to \< 92% on Day 15 are reported.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, pulse rate, and body temperature).
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of general biochemistry, hematology, and urinalysis.
Number of participants with abnormal ECGs reported as TEAEs are reported.
The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).
Number of participants with clinically significant findings in physical and neurological examinations are reported.
Male hormone levels investigated included testosterone, luteinizing hormone, follicle stimulating hormone, and inhibin B. Number of Participants with abnormal male hormone levels as assessed by the investigator are reported.
Number of participants experiencing any adverse event
Number of participants experiencing any treatment emergent adverse events
Number of participants experiencing any treatment-related TEAEs
Number of participants experiencing any moderate TEAEs
Number of participants experiencing any treatment-related moderate TEAEs
Number of participants experiencing any severe TEAEs
Number of participants experiencing any treatment-related severe TEAEs
Number of participants experiencing any serious adverse events (SAEs)
Number of participants experiencing any treatment-related serious adverse events (SAEs)
Number of participants with treatment-emergent adverse events leading to early discontinuation
Number of participants who died
Number of participants with treatment-related abnormal vital signs considered clinically significant or reported as a treatment-emergent adverse event by the investigator.
Number of participants with treatment-related abnormal blood pressure considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of participants with treatment-related abnormal heart rate considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Measured by standing pulse rate at baseline and 2 hours post
Number of participants with treatment-related abnormal hematology values considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of participants with treatment-related abnormal serum chemistry values considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of participants with treatment-related abnormal urinalysis values considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of participants with abnormal 12-lead electrocardiograms (ECGs), considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Measured by digital electrocardiograms (ECGs)
PR interval is the time from the beginning of atrial depolarization to the onset of ventricular depolarization. Measured by digital electrocardiograms (ECGs)
QRS complex represents the electrical impulse as it spreads through the ventricles and indicates ventricular depolarization. Measured by digital electrocardiograms (ECGs)
The QT interval is measured from the beginning of the QRS complex to the end of the T wave and primarily represents the return of stimulated ventricles to their resting state (ventricular repolarization). Measured by digital electrocardiograms (ECGs)
The QTcF if the QT interval corrected for heart rate using Fridercia's formula. Measured by digital electrocardiograms (ECGs)
The RR interval the time elapsed between two successive R waves of the QRS signal on the electrocardiogram. Measured by digital electrocardiograms (ECGs)
Number of participants with abnormal testosterone levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of participants with abnormal luteinizing hormone (LH) levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of participants with abnormal follicle stimulating hormone (FSH) levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator
Number of participants with abnormal Inhibin B levels test results, considered clinically significant or reported as a treatment-emergent adverse event by the investigator
| Arm | Type | Description |
|---|---|---|
| Morphine then AZD4041 then Morphine + AZD4041 | EXPERIMENTAL | Participants will receive a single intravenous (IV) dose of morphine Dose Level 1 on Day 1. From Day 2 to Day 15, participants will receive an oral dose of AZD4041 Dose Level 1, once daily for 14 consecutive days. On Day 15, participants will receive an oral dose of AZD4041 Dose Level 1 in combination with a single IV dose of morphine Dose Level 1. |
| Morphine then Placebo then Morphine + Placebo | PLACEBO_COMPARATOR | Participants will receive a single IV dose of morphine Dose Level 1 on Day 1. From Day 2 to Day 15, participants will receive an oral dose of placebo matched to AZD4041, once daily for 14 consecutive days. On Day 15, participants will receive an oral dose of placebo matched to AZD4041 in combination with a single IV dose of morphine Dose Level 1. |
| Cohort 1: AZD4041 Dose Level 1 | EXPERIMENTAL | Participants will receive oral solution of AZD4041 dose level 1 once daily (QD) directly into the mouth using a syringe from Days 1 to 14. |
| Cohort 2: AZD4041 Dose Level 2 | EXPERIMENTAL | Participants will receive oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14. |
| Cohort 3: AZD4041 Dose Level 3 | EXPERIMENTAL | Participants will receive oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14. |
| Cohorts 1-3: Pooled Placebo | PLACEBO_COMPARATOR | Participants will receive oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14. |
| AZD4041 | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Morphine | DRUG | Participants will receive IV dose of Morphine as stated in arm description. |
| AZD4041 | DRUG | Participants will receive oral doses of AZD4041 as stated in arm description. |
| Placebo | OTHER | Participants will receive oral doses of placebo as stated in arm description. |
Inclusion Criteria: 1. Recreational opioid user, not currently considered to have moderate or severe substance use disorder for opioids (based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition \[DSM-5\] criteria) and has experience with opioid use for non-therapeutic purpose...
AZD4041 is an investigational small molecule being developed by AstraZeneca PLC for opioid use disorder and smoking cessation. It is in Phase 1 clinical development and has been studied in placebo-controlled, double-blind trials in healthy volunteers and recreational opioid users. It has not been approved by the FDA.
AZD4041 is being developed for opioid use disorder and smoking cessation. Clinical trials have enrolled healthy volunteers and recreational opioid users to assess safety, tolerability, pharmacokinetics, and effects on respiratory drive. The drug remains investigational and is not approved for any indication.
AZD4041 is developed by AstraZeneca PLC, which trades on the Nasdaq under the ticker AZN. AstraZeneca is the sponsor of the clinical program evaluating the drug in opioid use disorder and smoking cessation.
AZD4041 is in Phase 1 clinical development. Three Phase 1 trials have been completed, including studies in healthy participants and recreational opioid users, with a combined enrollment of 81 participants. The trials were randomized, double-blind, and placebo-controlled. AZD4041 is investigational and has not been approved by the FDA.
AZD4041 has been evaluated in three completed Phase 1 trials. NCT05587998 assessed the effect of AZD4041 on respiratory drive in recreational opioid users in the United States. NCT05233085 was a safety study in healthy participants in Canada, and NCT04076540 assessed safety, tolerability, and pharmacokinetics in healthy volunteers in the United States.
AZD4041 is a small molecule developed for opioid use disorder and smoking cessation. Its specific molecular target has not been disclosed in the available clinical trial information, which focused on safety, tolerability, pharmacokinetics, and respiratory drive effects in healthy volunteers and recreational opioid users.