A Study to Test How Either a Capsule or a Tablet With NDec (Decitabine and Tetrahydrouridine) Works in the Body of Healthy People

A Study to Investigate the Pharmacokinetics and Pharmacodynamics of a Single Oral Dose of Decitabine and Tetrahydrouridine (NDec) When Administered Either as a Modified Release Formulation or an Immediate Release Formulation in Healthy Participants

This study will look at two different oral formulations and compare them. The medicine in the study is called NDec and it is a combination of two medicines (decitabine and tetrahydrouridine). Both medicines are new for the treatment of sickle cell disease, a rare blood disease. The purpose of the study is to compare the absorption of two different NDec versions (a tablet and a capsule). Participant will either get first the tablet and then the capsule, or the other way around. The order in which participant get them is decided by chance. The study will last for about 12 to 45 days depending on the wash-out period between the two stays in the clinic and from recruitment to the first study day.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Decitabine-THU; Drug: Decitabine-THU

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil Institut für Stoffwechselforschung GmbH
• United States
  • Utah
    • Millcreek, Utah, United States, 84124
      • ICON-Salt Lake City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
• Male or female.
• Age 18 64 years (both inclusive) at the time of signing the informed consent.
• Body weight between 60.0 and 100.0 kilogram (kg) (both inclusive) at screening.
• Body mass index between 18.5-29.9 kilograms per square meter (kg/m^2) (both inclusive).
• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

• Platelet count greater than (>) 400*10^9/ Liter (L) at visit 1
• Absolute neutrophil count less than or equal to (≤) 1.5*10^9/L at visit 1

• Female who is:

  1. pregnant, breast-feeding or intends to become pregnant during the trial or within 6 months after the last dose of trial product or
  2. of childbearing potential and not using highly effective contraceptive method and whose male partner is not using effective contraception, from screening until 6 months after the last dose of trial product
• Male of reproductive age with female partner of childbearing potential who does not agree to use condoms and whose female partner of childbearing potential is not using a highly effective contraceptive measure (or adequate contraceptive measure as required by local regulation or practice) from signing the informed consent form (ICF) until 6 months after the last dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Formulation A followed by Formulation B; Participants will receive a single oral dose of decitabine and tetrahydrouridine (THU) immediate release tablets (Formulation A) on Day 1 of treatment period 1 followed by a single oral dose of decitabine and THU delayed release capsules (Formulation B) on Day 1 of treatment period 2. A washout period of 7- 21 days will be maintained between the two treatment periods.	Drug: Decitabine-THU; Orally administered immediate release tablets.; Other Names: NDec; Drug: Decitabine-THU; Orally administered delayed release capsules.; Other Names: NDec
Experimental: Formulation B followed by Formulation A; Participants will receive a single oral dose of decitabine and THU delayed release capsules (Formulation B) on Day 1 of treatment period 1 followed by a single oral dose of decitabine and THU immediate release tablets (Formulation A) on Day 1 of treatment period 2. A washout period of 7- 21 days will be maintained between the two treatment periods.	Drug: Decitabine-THU; Orally administered immediate release tablets.; Other Names: NDec; Drug: Decitabine-THU; Orally administered delayed release capsules.; Other Names: NDec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf,DEC,SD: Area under the plasma decitabine concentration-time curve after a single dose	Measured in hours*nanogram per milliliter (h*ng/mL).	Predose (Day 1) up to 48 hours post dose (Day 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf,THU,SD: Area under the plasma tetrahydrouridine concentration-time curve after a single dose	Measured in h*ng/mL.	Predose (Day 1) up to 48 hours post dose (Day 3)
Cmax,DEC,SD: Maximum plasma concentration of decitabine after a single dose	Measured in nanogram per milliliter (ng/mL).	Predose (Day 1) up to 48 hours post dose (Day 3)
Cmax,THU,SD: Maximum plasma concentration of tetrahydrouridine after a single dose	Measured in ng/mL.	Predose (Day 1) up to 48 hours post dose (Day 3)
t½,DEC,SD: Terminal half-life for decitabine after a single dose	Measured in hours.	Predose (Day 1) up to 48 hours post dose (Day 3)
t½,THU,SD: Terminal half-life for tetrahydrouridine after a single dose	Measured in hours.	Predose (Day 1) up to 48 hours post dose (Day 3)
tmax,DEC,SD: Time to maximum observed plasma decitabine concentration after a single dose	Measured in hours.	Predose (Day 1) up to 48 hours post dose (Day 3)
tmax,THU,SD:: Time to maximum observed plasma tetrahydrouridine concentration after a single dose	Measured in hours.	Predose (Day 1) up to 48 hours post dose (Day 3)
Maximum change from pre dose in dNA methyltransferase 1 (DNMT1) protein expression after a single dose	Measured in mean fluorescence intensity (MFI).	Predose (Day 1) up to 48 hours post dose (Day 3)
Maximum change from pre dose in cytidine deaminase (CDA) activity after a single dose	Measured in micromoles per liter per minute (µmol/L/min).	Predose (Day 1) up to 48 hours post dose (Day 3)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Estimated): February 27, 2024
• Primary Completion (Estimated): July 11, 2024
• Study Completion (Estimated): July 11, 2024

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Estimated): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: NN7533-7587; U1111-1285-7491 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No