Study of the Safety, Tolerability, and Pharmacokinetics of NUV001 Administered Orally to Healthy Adult Participants

NCT06133478 | Completed Phase 1 FDA Drug

• 1 other identifier: NUV 001-CLI-001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This blinded placebo-controlled study is designed to evaluate the safety, tolerability, and PK in healthy participants of a single- and multiple-doses (SAD and MAD) of a new investigational drug: NUV001

Conditions

Healthy Volunteers

Keywords

Phase 1; Single ascending dose (SAD); Multiple ascending dose (MAD); Safety; Tolerance; Pharmacokinetics

Outcome Measures

Primary Outcomes (6)

• Safety as measured by subject incidence of treatment-emergent adverse events (SAD/MAD)

  Percentage of Participants Who Experienced Any Adverse Events.

  SAD: First dose date (treatment period 1 Day 1) plus 1 day (until discharge), MAD: First dose date (treatment period 2 Day 1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit).

• Safety as measured by subject incidence of treatment-emergent clinically significant changes in vital signs (SAD/MAD)

  Subject incidence of treatment-emergent clinically significant changes in vital signs (Systolic and Diastolic Blood Pressure in millimeters of mercury (mmHg), Heart Rate in beats per minute (bpm), and Oral Body temperature in Celsius).

  SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit).

• Safety as measured by subject incidence of treatment-emergent clinically significant changes in Electrocardiograms (SAD/MAD)

  Subject incidence of treatment-emergent clinically significant changes in 12-lead ECGs (PR interval in milliseconds (msec), QRS duration in milliseconds (msec), QRS axis in milliseconds (msec), QT interval in milliseconds (msec)).

  SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit).

• Safety as measured by subject incidence of treatment-emergent clinically significant changes in Blood safety tests (SAD/MAD)

  Subject incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests (Complete Blood Count (absolute counts and %), Fasting blood glucose concentration and Serum concentrations in Electrolytes, Protein, Albumin, Total Bilirubin, Blood urea nitrogen, Creatinine, Aspartate Aminotransferase, Alanine Aminotransferase, estimated Glomerular Filtration Rate (eGFR using CKD EPI equation, Activated partial thromboplastin time (aPTT) and Prothrombin Time test (PT) with International Normalized Ratio (INR)).

  SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit).

• Safety as measured by subject incidence of treatment-emergent clinically significant changes in Urinalysis safety tests (SAD/MAD)

  Subject incidence of treatment-emergent clinically significant changes in Urinalysis safety tests (pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase).

  SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit).

• Safety as measured by subject incidence of treatment-emergent clinically significant changes in Weight (SAD/MAD)

  Subject incidence of treatment-emergent clinically significant changes in Weight in kilograms (Kg).

  SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit).

Secondary Outcomes (6)

• NUV001 concentration in whole blood (SAD/MAD)

  Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12

• NUV001 metabolite A concentration in whole blood (SAD/MAD)

  Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12

• NUV001 metabolite B concentration in plasma (SAD/MAD)

  Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12

• NUV001 metabolite C concentration in plasma (SAD/MAD)

  Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12

• NUV001 metabolite C concentration in urine (SAD/MAD)

  Treatment period 1 (SAD) : collection at Predose and during intervals 0-6, 6-12 and 12-24 hours on Day 1 ; Treatment period 2 (MAD) : collection at Predose and during intervals 0-6, 6-12 and 12-24 hours on Days 1 and 14

Study Arms (2)

NUV001 active

EXPERIMENTAL

Single oral administration (treatment period 1 - SAD) and after a washout of at least 5 days, repeated once daily (q.d.) administrations for 14 days (treatment period 2 - MAD)

Drug: NUV001 active cohort 1; Drug: NUV001 active cohort 2; Drug: NUV001 active cohort 3; Drug: NUV001 active cohort 4

NUV001 Placebo

PLACEBO COMPARATOR

Single oral administration (treatment period 1 - SAD) and after a washout of at least 5 days, repeated once daily (q.d.) administrations for 14 days (treatment period 2 - MAD)

Drug: NUV001 placebo cohort 1; Drug: NUV001 placebo cohort 2; Drug: NUV001 placebo cohort 3; Drug: NUV001 placebo cohort 4

Interventions

NUV001 active cohort 1 DRUG

6 participants will be assigned to receive active treatment

Also known as: NUV001 A mg

NUV001 active

NUV001 active cohort 2 DRUG

6 participants will be assigned to receive active treatment

Also known as: NUV001 B mg

NUV001 active

NUV001 active cohort 3 DRUG

6 participants will be assigned to receive active treatment

Also known as: NUV001 C mg

NUV001 active

NUV001 active cohort 4 DRUG

6 participants will be assigned to receive active treatment

Also known as: NUV001 D mg

NUV001 active

NUV001 placebo cohort 1 DRUG

2 participants will be assigned to receive placebo

NUV001 Placebo

NUV001 placebo cohort 2 DRUG

2 participants will be assigned to receive placebo

NUV001 Placebo

NUV001 placebo cohort 3 DRUG

2 participants will be assigned to receive placebo

NUV001 Placebo

NUV001 placebo cohort 4 DRUG

2 participants will be assigned to receive placebo

NUV001 Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female 18 to 55 years of age inclusive, at screening.
• A body mass index (BMI) between 18.00 and 30.00 kg/m² inclusive and a body weight between 60 kg and 100 kg for males (inclusive), and 50 kg and 100 kg for females (inclusive).
• Healthy as determined by the investigator based on medical history, physical examination findings, clinical laboratory test results, and digital 12 lead ECG readings (all results should be normal or, if out of range, non-clinically significant as determined by the Investigator).
• Vital signs at Screening and Admission are within the following ranges:
• Systolic blood pressure 90-140 mmHg (inclusive);
• Diastolic blood pressure 50-90 mmHg (inclusive);
• Heart rate 40-100 beats per minute (inclusive);
• Oral temperature 36.0-37.5°C (inclusive);
• AST, ALT, and Total bilirubin are \<1.5 x ULN Screening and Admission.
• Serum creatinine is \<1.5 mg/dL and estimated glomerular filtration rate is ≥60 mL/min/1.73 m2 based on Chronic Kidney Disease Epidemiology Collaboration at Screening and Admission.
• QTcF is ≤450 ms for males and ≤470 ms for females at Screening and Admission.
• Non-smoker and no use of tobacco or nicotine-containing products for 6 months prior to screening.
• Have a high probability for compliance with and completion of the study.
• Female participants of childbearing potential \[meaning who are not either surgically sterile (bilateral tubal ligation/occlusion, bilateral salpingectomy, bilateral oophorectomy or hysterectomy) or post-menopausal (no spontaneous menstrual periods for at least two years), confirmed by serum follicle stimulating hormone \[FSH\] in post-menopausal range based on laboratory reference range, must commit to using a highly effective method of birth control and throughout the entire study and for 90 days after last dose of study drug:
• Combined hormonal estrogen and progestogen-containing, or progestogen-only hormonal contraception associated with inhibition of ovulation, started at least 4 weeks prior to the dosing and condom with spermicide for the male partner.

You may not qualify if:

• Medical History
• Any significant cardiovascular (e.g., heart failure), hepatic, renal, respiratory (e.g., asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidemia), immunologic, dermatological, hematological, neurologic, psychiatric disease or history of any clinically important drug allergy.
• Acute disease state (e.g., vomiting, fever, diarrhea) within 7 days before Day 1 of Treatment Period 1 (SAD).
• Pregnant or lactating female.
• Inability to follow study procedures.
• Use of recreational drugs within 1 year before Day 1 of Treatment Period 1 (SAD).
• History of alcoholism within 1 year before Day 1 of Treatment Period 1 and/or Regular alcohol consumption \>14 units of alcohol per week (1 unit = ½ pint \[approximately 240 mL\] beer, 25 mL of 40% spirit or a 125 mL glass of wine) within 3 months prior to the admission.
• Donation of blood or blood loss (i.e., \> 400 mL) within 90 days before Day 1 of Treatment Period 1 (SAD).
• Known allergy or intolerance to study drug, or excipients present in drug product.
• Physical and Laboratory Findings
• Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening.
• Positive findings of urine drug screen \[methadone, barbiturates, oxycodone, amphetamines, methamphetamines, opiates, cannabinoids, cocaine, benzodiazepines, tricyclic antidepressants (TCA), 3,4-methylenedioxy-methamphetamine (MDMA; ecstasy), phencyclidine, cotinine\] at screening or admission.
• Positive Covid -19 by rapid antigen test at admission.
• Prohibited Treatments and study restrictions:
• Use of any investigational drug within 30 days before study drug administration on Day 1 of Treatment Period 1 (SAD) except for medications needed to treat Adverse Events.

Sponsors & Collaborators

• Nuvamid SA: lead
• Medpace, Inc.: collaborator
• LGD: collaborator
• Anapharm: collaborator

Study Sites (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

Study Officials

• Mary Beth Brune, MD

  Medpace, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2023
• First Posted: November 15, 2023
• Study Start: November 9, 2023
• Primary Completion: March 1, 2024
• Study Completion: April 5, 2024
• Last Updated: May 28, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)