Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03436316 | A Study to Evaluate the Safety, Tolerability and Absorption to the Blood After Administration of Single and Multiple Doses of AZD8154 in Healthy Participants. | PHASE1 | COMPLETED | 78 | — | — | Jul 26, 2018 | Jul 29, 2019 | Aug 8, 2019 | 1 | Germany |
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses; inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess white blood cell count (WBC), red blood cell count (RBC), neutrophils absolute count, lymphocytes absolute count, monocytes absolute count, eosinophils absolute count, basophils absolute count as a variable of safety and tolerability of AZD8154 following inhaled administration of single ascending doses and inhaled and intravenous (IV) administration of single doses to healthy participants to healthy participants.
To assess white blood cell count (WBC), red blood cell count (RBC), neutrophils absolute count, lymphocytes absolute count, monocytes absolute count, eosinophils absolute count, basophils absolute count the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses and inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants. The brief physical examinations will include an assessment of the general appearance, skin, cardiovascular system, respiratory and abdomen.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants. The brief physical examinations will include an assessment of the general appearance, skin, cardiovascular system, respiratory and abdomen.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy subjects. The brief physical examinations will include an assessment of the general appearance, skin, cardiovascular system, respiratory and abdomen.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess serum level of sodium, potassium, calcium, and phosphate as a variable of safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess serum level of sodium, potassium, calcium, and phosphate as a variable of safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess serum level of sodium, potassium, calcium, and phosphate as a variable of safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.
The DLCO assessment will be performed in Part 1 of the study. The DLCO assessments will be performed in Part 2, only if emerging data in Part 1 indicates that it is needed. The DLCO should be performed according to the American thoracic society (ATS)/ European respiratory society (ERS) guidelines. Post dose DLCO will only be performed if a reduction is observed in FEV1 or FVC (≥ 12%) starting 6 hours after IMP administration.
The DLCO assessments will be performed in Part 2 and Part 3, only if emerging data in Part 1 indicates that it is needed. The DLCO should be performed according to the ATS/ERS guidelines. Post dose DLCO will only be performed if a reduction is observed in FEV1 or FVC (≥ 12%) starting 6 hours after IMP administration.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants. The laboratory variables to be measured are: total bilirubin, unconjugated bilirubin, thyroxine (T4), thyroid stimulating hormone (TSH), triglycerides, follicle stimulating hormone (FSH), creatinine, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cystatin C, gamma glutamyl transpeptidase, and urea.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants. The laboratory variables to be measured are: total bilirubin, unconjugated bilirubin, thyroxine (T4), thyroid stimulating hormone (TSH), triglycerides, follicle stimulating hormone (FSH), creatinine, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cystatin C, gamma glutamyl transpeptidase, and urea.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy subjects. The laboratory variables to be measured are: total bilirubin, unconjugated bilirubin, thyroxine (T4), thyroid stimulating hormone (TSH), triglycerides, follicle stimulating hormone (FSH), creatinine, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cystatin C, gamma glutamyl transpeptidase, and urea.
To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants. The laboratory variables to be measured are: protein, glucose, and blood.
To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants. The laboratory variables to be measured are: protein, glucose, and blood.
To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy subjects. The laboratory variables to be measured are: protein, glucose, and blood.
| Arm | Type | Description |
|---|---|---|
| SAD Cohort 1 (Part 1) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled small particle dose 1) and 2 participants will receive placebo. |
| SAD Cohort 2 (Part 1) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled small particle dose 2) and 2 participants will receive placebo. |
| SAD Cohort 3 (Part 1) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled small particle dose 3) and 2 participants will receive placebo. |
| SAD Cohort 4 (Part 1) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled small particle dose 4) and 2 participants will receive placebo. |
| SAD Cohort 5 (Part 1) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled small particle dose 5) and 2 participants will receive placebo. Participants in this Cohort will return for a second Treatment Period after a minimum washout period of 7 to 14 days. All 6 subjects will receive an inhaled dose of AZD8154 (large particle size). |
| SAD Cohort 6 (Part 1) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled small particle dose 6) and 2 participants will receive placebo. |
| Cohort 1 (Part 2) | EXPERIMENTAL | All participants in this cohort will receive single IV dose of AZD8154 in Treatment Period 1 and then after washout period, will receive inhaled AZD8154 (small particle size) in Treatment Period 2. |
| MAD Cohort 1 (Part 3) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled dose 8) and 2 participants will receive placebo on Day 1. Participants will then receive multiple dosing of AZD8154 (inhaled dose 8) or placebo once daily from Day 4 to Day 12. |
| MAD Cohort 2 (Part 3) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled dose 9) and 2 participants will receive placebo on Day 1. Participants will then receive multiple dosing of AZD8154 (Inhaled dose 9) or placebo once daily from Day 4 to Day 12. |
| MAD Cohort 3 (Part 3) | EXPERIMENTAL | 6 Participants will receive AZD8154 (single inhaled dose 10) and 2 participants will receive placebo on Day 1. Participants will then receive multiple dosing of AZD8154 (inhaled dose 10) or placebo once daily from Day 4 to Day 12. |
| Name | Type | Description |
|---|---|---|
| AZD8154 | DRUG | SAD Part 1; 6 cohorts which receive single dosing. One cohort is invited back for large particle administration. Part 2; 1 cohort which receives IV dose and then inhaled administration of AZD8154. MAD Part 3; 3 cohorts will receive inhaled multiple dosing. Additional doses are provisional and could be adjusted based on the emerging data from the previous dose by the safety review committee (SRC). |
Inclusion Criteria: 1. Provision of signed and dated, written informed consent before any study specific procedures. 2. Healthy male and/or female participants of non-childbearing potential aged 18 to 45 years (inclusive at the Screening Visit) with suitable veins for cannulation or repeated venipu...