DS-2741a Phase I Study- A Three-part First-in-human Study: Single Ascending Dose and Multiple Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of DS-2741a After Subcutaneous Injection in Healthy Japanese Male Subjects, and Single Dose Study to Assess the Pharmacokinetics, Safety, Pharmacodynamics and Efficacy of DS-2741a After Subcutaneous Injection in Japanese Subjects With Moderate to Severe Atopic Dermatitis.
Overview
- Phase
- Phase 1
- Intervention
- DS-2741a
- Conditions
- Atopic Dermatitis
- Sponsor
- Daiichi Sankyo Co., Ltd.
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3)
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a phase 1, single-center, first-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of DS-2741a after subcutaneous injection in healthy Japanese male volunteers and Japanese participants with moderate to severe atopic dermatitis.
Detailed Description
This study consists of three parts. Part 1 and Part 3 are a single ascending and multiple dose study to assess the safety, pharmacokinetics and pharmacodynamics of DS-2741a after subcutaneous injection in healthy Japanese male participants. Part 2 is a single-dose study to assess the pharmacokinetics, safety, pharmacodynamics and efficacy of DS-2741a after subcutaneous injection in Japanese participants with moderate to severe atopic dermatitis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For Part 1 and Part 3:
- •Japanese healthy male subjects.
- •Age ≥20 and ≤45 years upon providing informed consent.
- •Body mass index (BMI) ≥18.5 and \<25.0 kg/m\^2 at screening.
- •For Part 2:
- •Japanese Male or female, Age ≥20 upon providing informed consent.
- •Diagnosed with chronic atopic dermatitis (AD) at least 3 years before screening and by the criteria of Hannifin and Rajka at screening.
Exclusion Criteria
- •For Part 1 and Part 3:
- •Having a history of atopic dermatitis
- •Having a history of hypersensitivity to drugs or other substances or being idiosyncratic
- •Having alcohol or drug dependence, etc.
- •For Part 2:
- •Having an active dermatological disease other than AD, which, in the investigator's opinion, would affect study assessments.
- •Having a history of serious disease in the study potentially endangering the participant, as judged by the investigator or sub-investigator.
- •Having a chronic or acute infection requiring treatment within 28 days before screening.
- •Having superficial skin infections within 7 days before screening.
- •Having a history of recurrent oral herpes and recurrent genital herpes.
Arms & Interventions
Part 1: DS-2741a Cohort 3, 50 mg
Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 50 mg.
Intervention: DS-2741a
Part 1: DS-2741a Cohort 4, 150 mg
Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 150 mg.
Intervention: DS-2741a
Part 1: DS-2741a Cohort 1, 5 mg
Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 5 mg.
Intervention: DS-2741a
Part 1: DS-2741a Cohort 2, 15 mg
Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 15 mg.
Intervention: DS-2741a
Part 1: DS-2741a Cohort 5, 500 mg
Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 500 mg.
Intervention: DS-2741a
Part 1: DS-2741a Cohort 6, 1000 mg
Participants will be randomized to receive a single, subcutaneous injection of DS-2741a 1000 mg.
Intervention: DS-2741a
Part 1: Placebo
Participants will be randomized to receive a single, subcutaneous injection of placebo.
Intervention: Placebo
Part 2: DS-2741a Cohort 1, X mg (based on results of Part 1)
Participants will receive a single, subcutaneous injection of DS-2741a X mg, where X mg will be based on the maximum tolerated dose identified in Part 1.
Intervention: DS-2741a
Part 2: DS-2741a Cohort 1, Y mg (based on results of Part 1)
Participants will receive a single, subcutaneous injection of DS-2741a Y mg, where Y mg will be based on the maximum tolerated dose identified in Part 1.
Intervention: DS-2741a
Part 3: DS-2741a Cohort 1, Z mg (based on results of Part 1)
Participants will be randomized to receive a receive a single, subcutaneous injection of DS-2741a Z mg, where Z mg will be based on the maximum tolerated dose identified in Part 1.
Intervention: DS-2741a
Part 3: Placebo
Participants will be randomized to receive a single, subcutaneous injection of placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of adverse events among participants receiving DS-2741a (Part 1 and Part 3)
Time Frame: Day 1 through end of study, up to 4 weeks
Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 2)
Time Frame: Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49
Secondary Outcomes
- Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Characterize pharmacokinetic parameter area under the curve from time 0 to last measurable time point (AUClast) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Characterize pharmacokinetic parameter total clearance (CL/F) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Characterize pharmacokinetic parameter area under the curve from time 0 to infinity (AUCinf) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4,Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Characterize pharmacokinetic parameter volume of distribution (Vz/F) of plasma DS-2741a (Part 1)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 11, Day 14, Day 17, Day 21, Day 28, Day 35, Day 42, Day 49)
- Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 1 and Part 2)(Day 1 (pre-dose), Day 28, Day 49)
- Incidence of adverse events among participants receiving DS-2741a (Part 2)(Day 1 through end of study, up to 4 weeks)
- Characterize pharmacokinetic parameter maximum plasma concentration (Cmax) of plasma DS-2741a (Part 3)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17)
- Characterize pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of plasma DS-2741a (Part 3)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17)
- Characterize pharmacokinetic parameter trough plasma concentration (Ctrough) of plasma DS-2741a (Part 3)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17)
- Characterize pharmacokinetic parameter area under the curve from time 0 to 168 h (AUC168h) of plasma DS-2741a (Part 3)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17)
- Characterize pharmacokinetic parameter area under the curve from time 0 to tau (504-672 h) (AUCtau) of plasma DS-2741a (Part 3)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17)
- Incidence of anti-drug antibodies (ADAs) against DS-2741a (Part 3)(Day 1 (pre-dose),Day 7 (pre-dose), Day 14 (pre-dose), Day 21 (pre-dose), Day 49, Day 63)
- Characterize pharmacokinetic parameter terminal elimination half-life (t1/2) of plasma DS-2741a (Part 3)(Day 1 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 3, Day 5, Day 7 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 10, Day 12, Day 14 (pre-dose, 2, 8, 24, 36 hours after the start of administration), Day 17)