NCT03436316

Brief Summary

This study is a Phase 1, first in human (FiH) study, consisting of 3 parts (Part 1, Part 2, and Part 3) in healthy male and female participants of non-childbearing potential, performed at a single study center. Part 1 of this study will be a randomized, single-blind, placebo-controlled, single ascending dose (SAD) in healthy male and female participants of non-childbearing potential. Six dose levels of AZD8154 are planned to be investigated. Depending on emerging data, 1 to 2 additional dose levels may be added at the discretion of the Sponsor. Furthermore, one dose level will be repeated using the same formulation of AZD8154 but with a larger particle size (Part 1 only). Part 2 of this study will be a single cohort, open-label, 2-period, study to compare a single inhaled dose of AZD8154 (small particle size) nebuliser suspension with a single IV dose of AZD8154. Part 3 will be a single blind placebo controlled, multiple ascending doses (MAD) sequential design study in healthy male and/or female subjects of non childbearing potential conducted at a single center. Part 3:Three (3) inhaled dose levels of AZD8154 are planned to be investigated. Depending on the emerging data, up to 2 additional inhaled dose levels may be added at the discretion of the Sponsor.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P75+ for phase_1 asthma

Timeline
Completed

Started Jul 2018

Typical duration for phase_1 asthma

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 12, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 19, 2018

Completed
5 months until next milestone

Study Start

First participant enrolled

July 26, 2018

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 29, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 29, 2019

Completed
Last Updated

August 8, 2019

Status Verified

July 1, 2019

Enrollment Period

1 year

First QC Date

February 12, 2018

Last Update Submit

August 7, 2019

Conditions

Keywords

Phosphoinositide 3-kinase (PI3K) inhibitorFirst-in-human (FiH) study

Outcome Measures

Primary Outcomes (62)

  • Number of participants with adverse events (Part 1 & 2)

    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.

    From Day-1 up to follow-up visit (6 days post final dose).

  • Number of participants with adverse events (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From Day-1 up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal findings in 12-lead digital electrocardiography (ECG) (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    At Treatment period (Days 1 to 3).

  • Number of participants with abnormal findings in 12-lead digital ECG (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    At Treatment Periods 1 and 2 (Days 1 to 3).

  • Number of participants with abnormal findings in 12-lead digital ECG (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    At Treatment period (Days 1 to 15).

  • Number of participants with abnormal pulse rate (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to the treatment period (Day -1, Days 1 to 3)

  • Number of participants with abnormal pulse rate (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening (Days -28 to -2) up to follow-up visit (6 ± 1 days post-dose)

  • Number of participants with abnormal pulse rate (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening (Days-28 to -2) up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal findings in telemetry (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    At Treatment Period (Days 1 to 3).

  • Number of participants with abnormal findings in telemetry (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    At Treatment Periods 1 (Days 1 to 3) and 2 (Days 1 to 3 and Day 4).

  • Number of participants with abnormal findings in telemetry (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    At Treatment Period (Days 1 to 15)

  • Number of participants with abnormal hematology (Part 1 & Part 2)

    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.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal hematology (Part 3)

    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.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal blood pressure (systolic and diastolic) (Part 1 & Part 2)

    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.

    From screening up to the treatment period (Day -1, Days 1 to 3)

  • Number of participants with abnormal blood pressure (systolic and diastolic) (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal findings in respiratory rate (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to the treatment period (Day -1, Days 1 to 3).

  • Number of participants with abnormal findings in respiratory rate (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal findings in respiratory rate (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal physical examination (Part 1)

    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.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal physical examination (Part 2)

    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.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal physical examination (Part 3)

    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.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal findings in oral body temperature (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment period (Day -1, Days 1 to 3).

  • Number of participants with abnormal findings in oral body temperature (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to Treatment Periods 1 and 2.

  • Number of participants with abnormal findings in oral body temperature (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Forced expiratory volume in 1 second (FEV1) (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    At Days-28 to -2, Day -1, Days 1 to 3.

  • FEV1 (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    At Days-28 to -2, Day -1, Days 1 to 3, and follow-up visit (6 ± 1 days post-dose).

  • FEV1 (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    At Days-28 to -2, Day -1, Days 1 to 12, and follow-up visit (7-10 days post final dose).

  • Forced vital capacity (FVC) (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    At Days-28 to -2, Day -1, Days 1 to 3.

  • FVC (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    At Days-28 to -2, Day -1, Days 1 to 3, and follow-up visit (6 ± 1 days post-dose).

  • FVC (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    At Days-28 to -2, Day -1, Days 1 to 12, and follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal electrolytes (Part 1)

    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.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal electrolytes (Part 2)

    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.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal electrolytes (Part 3)

    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.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal hemoglobin (Hb) (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal hemoglobin (Hb) (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal hemoglobin (Hb) (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal hematocrit (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal hematocrit (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal hematocrit (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal mean corpuscular volume (MCV) (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal mean corpuscular volume (MCV) (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal mean corpuscular volume (MCV) (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal mean corpuscular hemoglobin (MCH) (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal mean corpuscular hemoglobin (MCH) (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal mean corpuscular hemoglobin (MCH) (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal mean corpuscular hemoglobin concentration (MCHC) (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal mean corpuscular hemoglobin concentration (MCHC) (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal mean corpuscular hemoglobin concentration (MCHC) (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal platelet count (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal platelet count (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal platelet count (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal reticulocytes absolute count (Part 1)

    To assess the safety and tolerability of AZD8154 following inhaled administration of single ascending doses to healthy participants.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal reticulocytes absolute count (Part 2)

    To assess the safety and tolerability of AZD8154 following inhaled and intravenous (IV) administration of single doses to healthy participants.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal reticulocytes absolute count (Part 3)

    To assess the safety and tolerability of AZD8154 following inhaled administration of multiple ascending doses to steady state to healthy participants.

    From screening up to follow-up visit (7-10 days post final dose).

  • Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) (Part 1 & Part 2)

    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.

    At Day -1, Days1 to 3 and follow-up visit (6 ± 1 days post-dose).

  • Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) (Part 3)

    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.

    At Day -1, Days 1 to 12, and follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal clinical chemistry (Part 1)

    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.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal clinical chemistry (Part 2)

    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.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal clinical chemistry (Part 3)

    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.

    From screening up to follow-up visit (7-10 days post final dose).

  • Number of participants with abnormal urinalysis (Part 1)

    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.

    From screening up to Treatment Period (Day-1, Days 1 to 3).

  • Number of participants with abnormal urinalysis (Part 2)

    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.

    From screening up to follow-up visit (6 ± 1 days post-dose).

  • Number of participants with abnormal urinalysis (Part 3)

    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.

    From screening up to follow-up visit (7-10 days post final dose).

Secondary Outcomes (27)

  • Observed maximum plasma concentration (Cmax)

    At treatment period [Days 1 to 3 (Part 1 & 2)], Day 4 (Part 2) and [Days 1 to 12 (Part 3)]

  • Time to reach peak or maximum observed concentration or response following drug administration (tmax)

    At treatment period [Days 1 to 3 (Part 1 & 2)], Day 4 (Part 2) and [Days 1 to 12 (Part 3)]

  • Terminal elimination rate constant (λz)

    At treatment period [Days 1 to 3 (Part 1 & 2)], Day 4 (Part 2) and [Days 1 to 12 (Part 3)]

  • Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz)

    At treatment period [Days 1 to 3 (Part 1 & 2)], Day 4 (Part 2) and [Days 1 to 12 (Part 3)]

  • Area under the plasma concentration time curve from time zero to 24 hours after dosing (AUC(0 24))

    At treatment period [Days 1 to 3 (Part 1 & 2)], Day 4 (Part 2) and [Days 1 to 12 (Part 3)]

  • +22 more secondary outcomes

Study Arms (10)

SAD Cohort 1 (Part 1)

EXPERIMENTAL

6 Participants will receive AZD8154 (single inhaled small particle dose 1) and 2 participants will receive placebo.

Drug: AZD8154

SAD Cohort 2 (Part 1)

EXPERIMENTAL

6 Participants will receive AZD8154 (single inhaled small particle dose 2) and 2 participants will receive placebo.

Drug: AZD8154

SAD Cohort 3 (Part 1)

EXPERIMENTAL

6 Participants will receive AZD8154 (single inhaled small particle dose 3) and 2 participants will receive placebo.

Drug: AZD8154

SAD Cohort 4 (Part 1)

EXPERIMENTAL

6 Participants will receive AZD8154 (single inhaled small particle dose 4) and 2 participants will receive placebo.

Drug: AZD8154

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).

Drug: AZD8154

SAD Cohort 6 (Part 1)

EXPERIMENTAL

6 Participants will receive AZD8154 (single inhaled small particle dose 6) and 2 participants will receive placebo.

Drug: AZD8154

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.

Drug: AZD8154

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.

Drug: AZD8154

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.

Drug: AZD8154

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.

Drug: AZD8154

Interventions

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).

Cohort 1 (Part 2)MAD Cohort 1 (Part 3)MAD Cohort 2 (Part 3)MAD Cohort 3 (Part 3)SAD Cohort 1 (Part 1)SAD Cohort 2 (Part 1)SAD Cohort 3 (Part 1)SAD Cohort 4 (Part 1)SAD Cohort 5 (Part 1)SAD Cohort 6 (Part 1)

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Provision of signed and dated, written informed consent before any study specific procedures.
  • 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 venipuncture.
  • Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of non-child-bearing potential, confirmed at Screening by fulfilling one of the following criteria: 3.1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and Follicle-stimulating hormone (FSH) levels in the postmenopausal range. 3.2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
  • Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive, and weigh at least 60 kg and no more than 100 kg inclusive.
  • Subject has a FEV1 ≥ 80% of the predicted value regarding age, height, gender and ethnicity at the Screening Visit.

You may not qualify if:

  • History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
  • Subject is immuno-compromised.
  • History of diabetes, impaired fasting glucose, metabolic syndrome, hypertriglyceridemia or familial lipid disorders.
  • Current or previous history of malignancy of any kind except cutaneous basal or squamous cell carcinoma successful treated with therapy.
  • History of any respiratory disorders such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF).
  • Subject with latent or active tuberculosis (TB), as conformed by a positive QuantiFERON® - TB Gold test or as judged by the Investigator at the Screening Visit.
  • History or presence of GI, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs, or bowel disorders not otherwise specified.
  • Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the (first) administration of the IMP.
  • Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results, defined as the following:
  • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> the upper limit of the normal (ULN) laboratory range.
  • Bilirubin \> 1.5 times the ULN laboratory range. 9.3. Absolute neutrophil count \< lower limit of normal (LLN). 9.4. Absolute lymphocyte count \< LLN. 9.5. Fasting plasma glucose \> ULN. 9.6. Triglycerides \> ULN.
  • Any positive result at the Screening Visit for serum hepatitis B surface antigen (HBsAg) OR hepatitis B core antibodies (anti-HBc), hepatitis C antibody and human immunodeficiency virus (HIV).
  • Abnormal vital signs, after 5 minutes supine rest, defined as any of the following:
  • Systolic BP \< 90 mmHg or \> 140 mmHg. 11.2. Diastolic BP \< 50 mmHg or \> 90 mmHg. 11.3. Heart rate \< 50 or \> 90 beats per minute (bpm).
  • Any clinically important abnormalities in rhythm, conduction or morphology of the 12-lead safety and any clinically important abnormalities in the 12-Lead dECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate using Fridericia's formula (QTcF) interval changes, including abnormal ST-T-wave morphology, particularly in the CSP defined primary lead for dECG analysis or left ventricular hypertrophy.
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

AsthmaHereditary Sensory and Autonomic Neuropathies

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System DiseasesNervous System MalformationsNervous System DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesPolyneuropathiesPeripheral Nervous System DiseasesNeuromuscular DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, Inborn

Study Officials

  • med. Rainard Fuhr, Dr

    PAREXEL Early Phase Clinical Unit Berlin

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
Part 1 of this study will be single-blind. Part 2 of this study will be open-label. Part 3 of this study will be single-blind.
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 12, 2018

First Posted

February 19, 2018

Study Start

July 26, 2018

Primary Completion

July 29, 2019

Study Completion

July 29, 2019

Last Updated

August 8, 2019

Record last verified: 2019-07

Data Sharing

IPD Sharing
Will not share

Locations