Active Ulcerative Colitis, Active Ulcerative Colitis (UC), Healthy Adult Volunteers
Conditions
Keywords
Mild-To-Moderate Active Ulcerative Colitis, Ulcerative Colitis, Active Ulcerative Colitis, active ulcerative colitis (UC)
Brief summary
This Phase 1b/2a clinical development plan is focused on the use of NP-201 acetate injection to investigate the pharmacokinetics (PK), safety, efficacy, PD (pharmacodynamic) markers (Phase 1b) and tolerability of NP-201 acetate injection after subcutaneous (SC) injection of multiple doses in healthy adults and in the ulcerative colitis (UC) patient population.
Detailed description
This Phase 1b/2a randomized, double-blinded study will be conducted in two parts - Phase 1b (Part A) in healthy volunteers and Phase 2a (Part B) in UC patients. This record relates only to Part A/Phase 1b study. This will be updated once Part A is complete. Part A (Multiple Ascending Doses-MAD): Up to a total of 32 healthy participants will be enrolled into four sequential cohorts (MAD1, MAD2, MAD3 and MAD4) and randomized 6:2 to receive either two dosing regimens of NP-201 acetate injection or placebo daily for 5 days or for MAD cohort 4 will be randomized 6:2 to receive 4 weekly doses of NP-201 acetate injection or placebo.
Interventions
DRUGNP-201 acetate injection (Part A)
Route of administration- Sub cutaneous. Dosage interval and frequency: MAD1-200mg daily for 5 days; MAD2- 300mg daily for 5 days, MAD3- 400mg daily for 5 days, MAD4- 400mg administered 4 weekly doses.
DRUGPlacebo
Matching placebo administered across Part A and Part B
Sponsors
NIBEC Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males and females, between 18 to 60 years inclusive, at the time of Screening. 2. Body mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2(inclusive), at Screening, with a minimum body weight of 50 kg 3. In good health based on the results of medical history, physical examinations, 12-lead ECG, vital signs measurement, and clinical laboratory evaluations at Screening, as assessed by the PI or designee. 4. All female participants of childbearing potential with male sexual partners and male participants with female sexual partners of childbearing potential must consent to use two highly effective methods of contraception from start of study and for at least 90 days (male and female participants) following the EOS visit or last dose of study treatment, whichever is later. Male participants must refrain from sperm donation from start of study and for 90 days after last dose of IP; female participants must refrain from donation of ova from start of study and for 30 days after last dose of IP. WOCBP must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Screening, and be willing to undergo additional pregnancy tests, as required, throughout the study. Women not of childbearing potential must be postmenopausal (defined as cessation of regular menstrual periods for at least 12 months without an alternative medical cause), confirmed by follicle-stimulating hormone (FSH) level \>40 IU/mL at Screening. 5. Participants whose smoking habit in the last 3 months prior to Screening included no more than 14 cigarettes per week (includes e-cigarettes and other nicotine and tobacco products) can be included in the study but must be willing to abstain from smoking from Screening until completion of the EOS visit (Part A only). 6. Ability and willingness to restrict the use of alcohol to ≤ 21 units per week for males and ≤ 14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits. Participants must have negative alcohol breath tests at Screening and Day -1 visits. 7. Participants who are able to receive SC injections specifically participants who have scars or tattoos in the area of concern. 8. Participants must participate voluntarily, sign the ICF, have good compliance, be able and willing to attend the necessary site visits and be willing to cooperate with follow-up visits. 9. No history of severe allergic or anaphylactic reactions, including known allergies or hypersensitivities to NP-201 acetate or its excipients.
Exclusion criteria
1. Have a clinically significant medical history or surgical history and have at least one of the following findings: 1. Have skin diseases that may affect the absorption of the IP (eg, psoriasis, contact dermatitis), scars, tattoos, and skin abnormalities that may interfere with SC injections, or a history of surgery within 60 days of Screening (except for simple appendectomy or hernia repair, as assessed by the PI or designee). 2. Have a recent significant history of kidney diseases, pancreatitis and/ or nephrolithiasis. 3. Participants with liver cirrhosis accompanying edema and/or ascites. 4. Have known clinically significant allergies as assessed by the PI or designee, diseases of either/or the cardiovascular system, peripheral vascular system, skin, mucous membranes, eyes, respiratory system, musculoskeletal system, and/or any other diseases that may pose a problem with the PK evaluation. History of childhood asthma can be included at the discretion of the PI or designee. 5. Presence of any underlying physical, or psychological medical condition that, in the opinion of the PI or designee, will make it unlikely that the participant will comply with the protocol, or complete the study per the protocol. 2. Pregnant or lactating at Screening or planning to become pregnant at any time during the study, including the follow-up period. 3. Have a clinically relevant history of hypersensitivity reactions or allergic reactions to drugs (such as aspirin and antibiotics), or known drug allergies (eg, to aspirin, nonsteroidal anti-inflammatory drugs \[NSAIDs\], antibiotics, iodine, anesthetics, other monoclonal antibodies, etc.). 4. Participants who have donated whole blood within 60 days prior to Screening or blood components within 30 days or received blood transfusion within 60 days. 5. Have received an IP or bioequivalence IP in another clinical study or bioequivalence study within 30 days prior to Screening or five half-lives prior to Screening. 6. Use of any prescription drugs within 14 days prior to dosing or non-prescription medications/products, including vitamins, minerals, and phyto-therapeutic/herbal/plant-derived preparations, alternative medicines, or dietary supplements within 7days prior to dosing (at the discretion of the PI or designee). The occasional use of paracetamol(up to 2g/day) is permitted. 7. History of alcoholism, substance or drug abuse-related disorders deemed significant by the PI or designee. 8. Participants with a positive toxicology screening panel. Positive test may be repeated once at the discretion of the investigator. 9. Have positive serology test (hepatitis B surface antigen \[HBsAg\], or hepatitis C virus antibody \[anti-HCV\], human immunodeficiency virus \[HIV\] test,) at Screening. 10. Active infection requiring medical treatment and/or isolation at the time of Screening. 11. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) \> 2.0 × upper limit of normal (ULN). 12. Bilirubin \> 1.5 × ULN (isolated bilirubin \> 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%). 13. QTcF \> 450 msec for male participants or QTcF \> 470 msec for female participants. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF). 14. Participants with corrected calcium (Ca) \> ULN, uric acid \> ULN, and/or estimated glomerular filtration rate \< 90 mL/min, calculated using Cockroft Gault formula. 15. Others who are ineligible to participate in this clinical study as determined by the PI or designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of NP-201 acetate injection in Healthy Volunteers. To evaluate the safety of NP-201 acetate injection by incidence, relationship and severity of adverse events (AE), serious adverse events and Treatment emergent AE | Part A-Screening to Day 12 post first dose administration | — |
| Safety of NP-201 acetate injection in Healthy Volunteers. To evaluate the safety of NP-201 acetate injection by changes in baseline Laboratory values | Part A-Screening to Day 12 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- AUC from time 0 to 24 (AUC24) | Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- AUC over the dosing interval (AUCtau) | Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Area under curve from 0 to last AUC(0-last) | Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Maximum plasma concentration at steadystate (Cmax,ss) | Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- time to Cmax,ss (tmax,ss) | Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Apparent oral body clearance at steady-state (CL/Fss) | Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Apparent volume of distribution at steady-state (Vd/Fss) | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection-Terminal half life (t1/2) | Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | — |
| Part A-Urine PK parameters of NP-201 acetate injection after multiple doses- cumulative amount of drug excreted in urine (Ae) | Part A-Samples collected on Day 1 and Day 5 post first dose administration | — |
| Part A-Urine PK parameters of NP-201 acetate injection after multiple doses- percent fraction of drug recovered in urine (Fe) | Part A-Samples collected on Day 1 and Day 5 post first dose adminstration | — |
| Part A-Urine PK parameters of NP-201 acetate injection after multiple doses- Renal clearance (CLr) | Part A-Samples collected on Day 1 and Day 5 post first dose adminstration | — |
| Area Under the Plasma Concentration-Time Curve (AUC) | Day 1, Day 8, Day 15, Day 22, Day 29, Day 30 (24 hours post-dose), Day 43 | Area under the plasma concentration-time curve (AUC) of NP-201 following subcutaneous administration at multiple dose levels. |
| Peak Plasma Concentration (Cmax) | Day 1, Day 8, Day 15, Day 22, Day 29, Day 30 (24 hours post-dose), Day 43 | Maximum observed plasma concentration (Cmax) of NP-201 following subcutaneous administration at multiple dose levels. |
| Time to Reach Maximum Plasma Concentration (Tmax) | Day 1, Day 8, Day 15, Day 22, Day 29 | Time to reach maximum plasma concentration (Tmax) of NP-201 following subcutaneous administration at multiple dose levels |
| Apparent Clearance (CL/F) | Day 30, Day 43 | Apparent clearance (CL/F) of NP-201 following subcutaneous administration at multiple dose levels. |
| Apparent Volume of Distribution (Vd/F) | Day 30, Day 43 | Apparent volume of distribution (Vd/F) of NP-201 following subcutaneous administration at multiple dose levels |
| Terminal Half-life (t½) | Day 30, Day 43 | Terminal elimination half-life (t½) of NP-201 following subcutaneous administration at multiple dose levels. |
| Renal Clearance (Clr) | Day 1 and Day 29 | Renal clearance (Clr) of NP-201 following subcutaneous administration at multiple dose levels. |
| Amount Excreted in Urine (Ae) | Day 1 and Day 29 | Total amount of NP-201 excreted in urine following subcutaneous administration at multiple dose levels. |
| Fraction of Dose Excreted in Urine (Fe) | Day 1 and Day 29 | Fraction of administered dose excreted in urine (Fe) following subcutaneous administration at multiple dose levels. |
| Part A-Immunogenicity (ADA) in Cohort MAD4 | Day 1 (pre-dose), Day 15, Day 29, and Day 43 | To assess presence of anti-drug antibodies following repeated weekly SC injections. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A- PK of NP-201 acetate injection metabolite- AUC from time 0 to 24 (AUC24) | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite Area under the concentration- time curve from 0 to 24hrs (AUC24) |
| Part A- PK of NP-201 acetate injection metabolite- AUC over the dosing interval (AUCtau) | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite Area under the concentration- time curve over the dosing interval (AUCtau) |
| Part A-PK of NP-201 acetate injection metabolite- Maximum plasma concentration at steady state (Cmax,ss) | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite maximum plasma concentration at steady state (CMAX, ss) |
| Part A- PK of NP-201 acetate Injection metabolite- Time to Cmax,ss (tmax,ss) | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite time to CMAX, ss (tmax, ss) |
| Part A-PK of NP-201 acetate injection metabolite- Apparent oral body clearance at steady state (CL/Fss) | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite apparent oral body clearance at steady state (CL/Fss) |
| Part A- PK of NP-201 acetate injection metabolite- Apparent volume of distribution at steady-state (Vd/Fss), | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite apparent volume distribution at steady state (Vd/Fss) |
| Part A-PK of NP-201 acetate Injection metabolite- terminal half-life (T1/2) | Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration | Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite terminal half-life (t1/2) |
| Part A-Metabolite PK parameters in Cohort MAD4-t½ | Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43 | To evaluate metabolite t½ (Apparent terminal half-life) |
| Part A-Metabolite PK parameters in Cohort MAD4-AUC | Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43 | To evaluate metabolite AUC (Area under the plasma concentration versus time curve) |
| Part A-Metabolite PK parameters in Cohort MAD4- Cmax | Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43 | To evaluate metabolite Cmax (Peak Plasma Concentration) |
| Part A-Metabolite PK parameters in Cohort MAD4- Tmax | Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43 | To evaluate metabolite Tmax (Time to maximum concentration) |
| Part A-Metabolite PK parameters in Cohort MAD4- CL/Fss | Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43 | To evaluate metabolite CL/Fss (Apparent clearance) |
| Part A-Metabolite PK parameters in Cohort MAD4- Vd/Fss | Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43 | To evaluate metabolite Vd/Fss (Apparent terminal volume of distribution) |
Countries
Australia
Contacts
PRINCIPAL_INVESTIGATORMichele DeSciscio, Dr.
CMAX Clinical Research Pty Ltd
Outcome results
None listed