A Study in Adult Males With X-linked Congenital Nephrogenic Diabetes Insipidus to Test the Effects of NDI-5001 Given for Multiple Days and to Test How NDI-5001 is Tolerated and Taken up in the Body

Phase 1RecruitingNCT07525960

Otsuka Pharmaceutical Development & Commercialization, Inc.24 enrolled

Overview

The primary purpose of this trial is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NDI-5001 administered as a capsule following daily oral dosing in adult males with X-linked congenital nephrogenic diabetes insipidus (NDI) due to vasopressin receptor Type 2 (V2R) mutations.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Insipidus

Interventions

NDI-5001DRUG

Capsule.

Medical Language ↔ Plain English

Inclusion Criteria 1. X-linked congenital NDI with a genotype-confirmed arginine vasopressin receptor 2 (gene) (AVPR2) mutation and no mutation in aquaporin-2 (AQP2). 2. Urine osmolality of ≤ 200 milliosmoles per kilogram of water (mOsm/kg) in a spot urine sample obtained from a first morning void upon awakening (at screening, check-in \[Day -4\], and Day -1) before consuming any food or drink after awakening. 3\) BMI between 18.0 to 32.0 kilograms per square meter (kg/m\^2), inclusive. Exclusion Criteria 1. Participant who is not willing to follow a low-sodium (\<=1 gram/day) diet during the in-clinic portion of the trial. 2. A positive drug screen for substances of abuse (including THC, cannabidiol) at screening or check-in. 3. Estimated glomerular filtration rate \<60 milliliters per minute per 1.73-kilogram square meters by serum creatinine and cystatin C at screening. 4. Participants who have taken an investigational drug within 30 days prior to screening. 5. Previous exposure to NDI-5001. 6. Any history of significant bleeding or hemorrhagic tendencies. Note: Other protocol-specified inclusion/exclusion criteria may apply.

Outcomes

Primary Outcomes

Percentage Change From Baseline in 24-Hour Urine Volume (Uvol)

Time frame: Up to Day 10

Percentage Change From Baseline in Spot Urine Osmolality (Uosm)

Time frame: Up to Day 10

Secondary Outcomes

Change From Time-Matched Baseline in Uvol

Time frame: Up to Day 10

Change From Time-Matched Baseline in Uosm

Time frame: Up to Day 10

Change From Baseline in 24-Hour Uosm

Time frame: Up to Day 10

Correlation Coefficient Between 24-Hour Uvol and Uvol by interval

Time frame: Up to Day 10

Correlation Coefficient Between 24-Hour Uvol and Uosm by Interval

Time frame: Up to Day 10

Correlation Coefficient Between 24-Hour Uvol and Spot Uosm

Time frame: Up to Day 10

Correlation Coefficient Between Change From Baseline in Uvol and Change From Baseline in Uosm by Interval

Time frame: Up to Day 10

Number of Participants With Adverse Events (AEs)

Time frame: Up to Day 39

Number of Participants With Clinically Relevant Changes in Clinical Laboratory Values

Time frame: Up to Day 31

Number of Participants With Potentially Clinically Relevant Changes in Vital Signs

Time frame: Up to Day 31

Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings

Time frame: Up to Day 10

Number of Participants With Potentially Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters

Time frame: Up to Day 10

Maximum (Peak) Plasma Concentration (Cmax) of NDI-5001

Time frame: Day 1 and Day 9

Time to Reach Maximum (Peak) Observed Plasma Concentration (Tmax) of NDI-5001

Time frame: Day 1 and Day 9

Area Under the Concentration-time Curve From Time Zero to 24 hours (AUC0-24h) of NDI-5001

Time frame: Up to 24 hours, post dose on Day 1 and Day 9

Dose-Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of NDI-5001

Time frame: Day 1 and Day 9

Dose-Normalized Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24h/Dose) of NDI-5001

Time frame: Up to 24 hours, post dose on Day 1 and Day 9

A Study in Adult Males With X-linked Congenital Nephrogenic Diabetes Insipidus to Test the Effects of NDI-5001 Given for Multiple Days and to Test How NDI-5001 is Tolerated and Taken up in the Body

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts