A Study to Evaluate the Safety of K-755 in Healthy Volunteers

NCT03414294 | Completed Phase 1

• 1 other identifier: K-755-1.01AU
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 study designed to explore the safety, tolerability and pharmacokinetics of K-755 following oral administration to healthy male and female volunteers.

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• Part A, B, C, D and E: Incidence and severity of Adverse Events

  A treatment-emergent adverse events (TEAE) will be summarized by treatment and overall, and summarized for each treatment by severity and relationship to study drug. All TEAEs leading to withdrawal, or SAEs, will be summarized.

  Up to 28 days after last administration

• Part A, B, C, D and E: Number of subjects with clinical laboratory test abnormalities

  The clinical laboratory will include hematology (hematocrit, hemoglobin, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, platelet count, red blood cell count, white blood cell count), clinical chemistry (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, calcium, chloride, cholesterol, creatinine, creatine phosphokinase, direct bilirubin, estimated glomerular filtration rate, gamma glutamyl transferase, glucose. inorganic phosphate, iron, lactate dehydrogenase, phosphorus, potassium, sodium, total bilirubin, total CO2, total protein, triglyceride, urea, uric acid), and urinalysis (bilirubin, blood, color and appearance, glucose, ketones, leukocyte esterase, nitrite, pH, protein, specific gravity, urobilinogen, microscopic examination, electrolytes). Abnormality will be determined by the investigator.

  Up to 28 days after last administration

• Part A, B, C, D and E: Number of subjects with vital signs abnormalities

  The vital sign will include blood pressure (mmHg), pulse rate (bpm), respiratory rate (breaths/min), and body temperature (degree Celsius). Abnormality will be determined by the investigator.

  Up to 28 days after last administration

• Part A, B, C, D and E: Number of subjects with clinically significant change in body weight

  Change in body weight (kg) at baseline and post dose will be measured. Clinical significance will be determined by the investigator.

  Up to 28 days after last administration

• Part A, B, C, D and E: Number of subjects with abnormal findings in physical examinations

  The physical examination will typically include general appearance, head and neck, eyes, ear, nose and throat, lymph nodes, thyroid, cardiovascular, respiratory, abdomen, nervous, skin, musculoskeletal, peripheral vascular and extremities and be performed at Investigator's discretion based on reported symptoms. Abnormality will be determined by the investigator.

  Up to 28 days after last administration

Secondary Outcomes (23)

• Part A: AUC0-inf of K-755

  Up to 28 days after single administration

• Part A: AUC0-tlast of K-755

  Up to 28 days after single administration

• Part A: Cmax of K-755

  Up to 28 days after single administration

• Part A: Tmax of K-755

  Up to 28 days after single administration

• Part A: t1/2 of K-755

  Up to 28 days after single administration

Study Arms (8)

K-755 Part A (SAD)

EXPERIMENTAL

Drug: K-755 Part A (SAD)

Placebo Part A (SAD)

PLACEBO COMPARATOR

Drug: Placebo Part A (SAD)

K-755 Part B (MAD)

EXPERIMENTAL

Drug: K-755 Part B (MAD)

Placebo Part B (MAD)

PLACEBO COMPARATOR

Drug: Placebo Part B (MAD)

K-755 Part C (FE)

EXPERIMENTAL

Drug: K-755 Part C (FE)

K-755 Part D (FE)

EXPERIMENTAL

Drug: K-755 Part D (FE)

K-755 Part E (MAD)

EXPERIMENTAL

Drug: K-755 Part E (MAD)

Placebo Part E (MAD)

PLACEBO COMPARATOR

Drug: Placebo Part E (MAD)

Interventions

K-755 Part A (SAD) DRUG

Single ascending dose (SAD). There will be 7 cohorts in the Part A. Three quarters of subjects will receive K-755 tablet orally in a double-blind fashion.

K-755 Part A (SAD)

Placebo Part A (SAD) DRUG

Single ascending dose (SAD). In Part A, one quarter of subjects will receive placebo tablet orally in a double-blind fashion.

Placebo Part A (SAD)

K-755 Part B (MAD) DRUG

Multiple ascending dose (MAD). There will be 4 cohorts in the Part B. Three quarters of subjects will receive K-755 oral tablet in a double-blind fashion.

K-755 Part B (MAD)

Placebo Part B (MAD) DRUG

Multiple ascending dose (MAD). In Part B, one quarter of subjects will receive placebo tablet orally in a double-blind fashion.

Placebo Part B (MAD)

K-755 Part C (FE) DRUG

Food effect (FE). All subjects in Part C will receive K-755 oral tablet both under fed and fasted condition in a open-label, crossover fashion.

K-755 Part C (FE)

K-755 Part D (FE) DRUG

Food effect (FE). All subjects in Part D will receive K-755 oral tablet both under fed and fasted condition in a open-label, crossover fashion.

K-755 Part D (FE)

K-755 Part E (MAD) DRUG

Multiple ascending dose (MAD). There will be 2 cohorts in the Part E. Three quarters of subjects will receive K-755 oral tablet in a double-blind fashion.

K-755 Part E (MAD)

Placebo Part E (MAD) DRUG

Multiple ascending dose (MAD). In the Part E. One quarter of subjects will receive placebo tablet orally in a double-blind fashion.

Placebo Part E (MAD)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
• Males or females, of any race, between 18 and 45 years of age.
• Body mass index (BMI) between 18.0 and 28.0 kg/m2.
• Hematology, clinical chemistry, and urinalysis test results within the reference ranges or showing no clinically relevant deviations, as judged by the Investigator.
• No clinically significant abnormalities on the basis of medical history, physical examination findings, and vital signs.
• All females must have a negative serum pregnancy test.
• Able and willing to comply with the protocol and study procedures.

You may not qualify if:

• Female subject who are pregnant or breastfeeding.
• Subject with presence of active or recurring clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease requiring medical treatment.
• Subject with any surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of K-755.
• Subject with presence of an active malignancy or within the past 5 years a malignancy of any type, other than basal cell carcinoma of the skin.
• Subject has a history of type 1 hypersensitivity to any medication and/or clinically relevant food allergies.
• Subject has a history of drug addiction.
• Subject has a positive screen for drugs of abuse, cotinine or alcohol.
• Subject has a history of regular alcohol consumption within 6 months of the study.
• Subject has smoked tobacco within 6 months prior to Check-in, or has used non-inhaled tobacco- or nicotine-containing products within 3 months prior to Check-in.
• Subject has used prescription or over-the-counter medications, dietary/nutritional supplements (except paracetamol or vitamin supplements)
• Subject has used steroid medications (oral, inhaled, parenteral, or topical) within 30 days or 5 half-lives (whichever is longer) before study drug administration.
• Subject has participated in an investigational drug study within 30 days or 5 half-lives (whichever is longer) before study drug administration.
• Subject has a positive screen for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 and 2 antigens/antibodies.
• Subject has had a clinically significant acute illness within 4 weeks or other illness within 5 days before the first study drug administration.
• Subject or a family member of the subject is a member of the professional or ancillary personnel working at the investigative site involved in the study.

Sponsors & Collaborators

• Kowa Company, Ltd.: lead

Study Sites (1)

CMAX, Clinical Research Pty Ltd

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Masking for Part A (SAD) , Part B (MAD), Part E (MAD) open for Part C (FE) and Part D (FE)
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential Assignment/Crossover (for food effect)

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 29, 2018
• Study Start: February 27, 2018
• Primary Completion: November 14, 2019
• Study Completion: November 14, 2019
• Last Updated: January 28, 2020

Record last verified: 2020-01

Locations

AU (1)