A Combined Single and Multiple Ascending Dose Study of ASP6858 in Healthy Subjects

NCT02359032 | Completed Phase 1

• 2 other identifiers: 6858-CL-00012014-003735-18
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is evaluate the safety and tolerability of single and multiple ascending oral doses of ASP6858. This study will also evaluate the pharmacokinetics (PK) of ASP6858 and its metabolites as well as the effect of food to the PK of ASP6858. The study will also evaluate the pharmacodynamics of ASP6858.

Conditions

Healthy Volunteers

Keywords

Healthy subjects; Pharmacokinetics of ASP6858; ASP6858; Pharmacodynamics of ASP6858

Outcome Measures

Primary Outcomes (7)

• Safety as assessed by adverse events

  Part 1 = up to 17 days; Part 2 = up to 50 days

• Safety as assessed by vital signs

  blood pressure, pulse rate, body temperature

  Part 1 = up to 17 days; Part 2 = up to 50 days

• Safety as assessed by clinical laboratory tests

  Biochemistry, hematology, urinalysis

  Part 1 = up to 17 days; Part 2 = up to 50 days

• Safety as assessed by 12-lead electrocardiogram (ECG)

  Part 1 = up to 17 days; Part 2 = up to 50 days

• Safety as assessed by continuous cardiac monitoring

  Part 1 = N/A for fasting cohort

  Part 1 = Days 1-4; Part 2 = Day 10

• Safety as assessed by coagulation parameters: aPTT, PT

  Activated partial thromboplastin time (aPTT); Prothrombin time (PT)

  Part 1 = up to 17 days; Part 2 = up to 50 days

• Safety as assessed by body weight (Part 2)

  up to 50 days

Secondary Outcomes (9)

• Secondary Outcome Title: Pharmacokinetic profile of ASP6858 (plasma): AUCinf, AUC5, AUC14, AUC24, AUClast, tlag, tmax, Cmax, t½, Vz/F, CL/F (Part 1)

  Day 1

• Pharmacokinetic profile of ASP6858 metabolite M1 and M2 (plasma): AUCinf, AUC5, AUC14, AUC24, AUClast, tlag, tmax, Cmax, t½, MPR (Part 1)

  Day 1

• Pharmacokinetic profile of ASP6858, metabolites M1 and M2 (urine): Ae24, Ae24%, Aelast, Aelast%, Aeinf, Aeinf%, CLR (Part 1)

  Day 1

• Pharmacokinetic profile of ASP6858 and metabolites M1 and M2 (plasma): Ctrough, morning (Part 2)

  Days 3, 6 and 9

• Pharmacokinetic profile of ASP6858 and metabolites M1 and M2 (plasma): tmax, Cmax, AUC5, PTR, AUC14, t1/2, AUC24 (Part 2)

  Day 10

Study Arms (5)

Part 1: ASP6858 single ascending dose

EXPERIMENTAL

ASP6858 arm

Drug: ASP6858

Part 1: Placebo single ascending dose

PLACEBO COMPARATOR

Placebo arm

Drug: Placebo

Part 1: ASP6858 single ascending dose (fasting cohort)

EXPERIMENTAL

ASP6858 arm

Drug: ASP6858

Part 2, Sequence 1: ASP6858 multiple ascending dose & placebo

EXPERIMENTAL

ASP6858 and placebo arm

Drug: ASP6858; Drug: Placebo

Part 2, Sequence 2: ASP6858 multiple ascending dose & placebo

EXPERIMENTAL

ASP6858 and placebo arm

Drug: ASP6858; Drug: Placebo

Interventions

ASP6858 DRUG

Oral tablets

Part 1: ASP6858 single ascending dose; Part 1: ASP6858 single ascending dose (fasting cohort); Part 2, Sequence 1: ASP6858 multiple ascending dose & placebo; Part 2, Sequence 2: ASP6858 multiple ascending dose & placebo

Placebo DRUG

Oral tablets

Part 1: Placebo single ascending dose; Part 2, Sequence 1: ASP6858 multiple ascending dose & placebo; Part 2, Sequence 2: ASP6858 multiple ascending dose & placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part 1: Healthy male subject, 18 to 55 years of age, inclusive, at screening. Part 2: Healthy male or female subject, 18 to 55 years of age, inclusive, at screening.
• Subject has a body mass index range of 18.5 to 30.0 kg/m2, inclusive, and weighs at least 50 kg, at screening.
• Subject has stable eating habits and weight (± 2 kg) over the last 4 weeks prior to screening.
• Subject is willing to comply strictly with the diet applied during the clinical study.
• Subject agrees not to participate in another interventional study while participating in the present clinical study, defined as signing the informed consent form until completion of the last study visit.

You may not qualify if:

• Subject had prior upper gastric, gastroduodenal, pancreatic or small intestinal surgery.
• Subject has lactose intolerance, gluten sensitivity or other condition with significant nutritional malabsorption.
• Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to ASP6858 or any components of the formulations used.
• Subject has any of the liver chemistry tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, gamma glutamyl transferase, total bilirubin \[TBL\]) above the upper limit of normal (ULN). In such a case the assessment may be repeated once on day -1 (in part 2: treatment period 1 only).
• Subject has any clinically significant history of allergic conditions.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to admission to the clinical unit (in part 2: treatment period 1 only).
• Subject has any clinically significant abnormality following the investigator's review of the physical examination, ECG and protocol-defined clinical laboratory tests at screening or admission to the clinical unit (in part 2: treatment period 1 only).
• Subject has a mean pulse \< 40 or \> 90 bpm; mean systolic blood pressure \> 140 mmHg; mean diastolic blood pressure \> 90 mmHg (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) at screening and day -1 (in part 2: treatment period 1 only). If the blood pressure exceeds the limits above, 1 additional triplicate can be taken.
• Subject has a mean corrected QT interval using Fridericia's formula \> 430 ms (for male subjects) and \> 450 ms (for female subjects) on day -1 (in part 2: treatment period 1 only). If these limits are exceeded, 1 additional triplicate ECG can be taken.
• Subject uses any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g/day) and except for use of contraceptives or hormone replacement therapy.
• Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit (in part 2: first admission).
• Subject has a history of drinking more than 21 units (male subjects) or 14 units (female subjects) of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) within 3 months prior to admission to the clinical unit (in part 2: first admission).
• Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit (in part 2: first admission).
• Subject uses any inducer of metabolism (e.g., barbiturates, rifampin) in 1 month prior to admission to the clinical unit (in part 2: first admission).

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Site GB44001

Harrow, HA1 3UJ, United Kingdom

Location

Study Officials

• Medical Director

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2015
• First Posted: February 9, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 21, 2016

Record last verified: 2016-05

Locations

GB (1)