A Bioequivalence Study Comparing Organic Phosphate (Sodium Glycerophosphate Injection) to Inorganic Phosphate (Sodium Phosphates Injection, USP)

Phase 1, Prospective, Single-Center, Randomized Sequence, Double-Blind, 2-Way Crossover Study Comparing Organic Phosphate (Sodium Glycerophosphate Injection) to Inorganic Phosphate (Sodium Phosphates Injection, USP)

This is a phase 1, prospective, single-center, randomized sequence, double-blind, 2-way crossover, relative bioavailability study in healthy adult subjects comparing Sodium Glycerophosphate Injection (SGP) to Sodium Phosphate Injection (NaP).

In this study it is planned to randomize approximately 42 healthy male and female subjects. All study periods will be completed during a single residency, the overall duration of residency will be 11 days (10 nights).

Study Overview

• Status: Completed
• Conditions: Parenteral Nutrition
• Intervention / Treatment: Drug: Sodium Glycerophosphate Injection; Drug: Sodium Phosphates Injection

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Austin PPD CRU

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Healthy males or non-pregnant, non-lactating healthy females.
2. Aged 18 to 55 years, inclusive, at the time of signing informed consent.
3. Body mass index (BMI) of 18.5 to 29.9 kg/m^2 and a minimum body weight of 57 kg as measured at screening.
4. Must be willing and able to comply with all study requirements including dietary requirements.
5. Subject must be literate, has signed a written informed consent form (ICF) and has the ability to communicate and comply with all study requirements
6. Must agree to use an adequate method of contraception.
7. Alkaline phosphatase level within standard reference range/normal limits at screening and admission.
8. Serum inorganic phosphate level within standard reference range/normal limits at screening and admission.
9. Serum parathyroid hormone (PTH) level within standard reference range/normal limits at screening.
10. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within reference range/normal limits at screening and admission.

Exclusion Criteria:

1. Subjects who have received any investigational medicinal product (IMP) in a clinical research study within 5 half-lives or within 30 days prior to first dose, whichever is longer.
2. Subjects who are study site or Sponsor employees, or subjects who are immediate family members of study site or Sponsor employees.
3. Subjects who have previously been administered IMP in this study.
4. History of any drug or alcohol abuse in the past 2 years prior to screening.
5. Regular alcohol consumption in 6 months prior to screening.
6. A confirmed positive alcohol urine test at screening or admission.
7. Current smokers or those who have smoked within the last 12 months prior to screening. A confirmed positive urine cotinine test at screening or first admission.
8. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months prior to screening.
9. Females of childbearing potential must have a negative pregnancy test (urine pregnancy test at screening). Females who are pregnant or lactating will be excluded.
10. Have poor venous access that limits phlebotomy.
11. Clinically significant abnormal clinical chemistry or hematology as judged by the Investigator.
12. Clinically significant abnormal urinalysis as judged by the Investigator.
13. History of diabetes mellitus (types I or II).
14. Prediabetes (fasting blood sugar level of >106 (repeat x 1 for confirmation of abnormal level).
15. Hypertriglyceridemia (fasting triglyceride level of > 200 mg/dL) at screening.
16. Subjects who, in the Investigator's opinion, have a clinically significant abnormal 12-lead resting ECG.
17. Positive drugs of abuse test result.
18. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
19. Evidence of renal impairment at screening, as indicated by an eGFR < 90mL/min/m^2.
20. History of any active systemic or immunologic disease, including but not limited to active renal, hepatic, hematological, gastrointestinal (except appendectomies/cholecystectomy), endocrinal, pulmonary (including asthma), cardiovascular, neurologic, or neurological disease (including demyelinating diseases such as multiple sclerosis), hypertension, tuberculosis, or systemic fungal infection.
21. History of bleeding ulcer, bleeding abnormalities or coagulation abnormalities.
22. History of hypophosphatasia.
23. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
24. Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Hay fever is allowed unless it is active.
25. Significant serious active skin disease, including rash, food allergy, eczema, psoriasis, or urticaria.
26. Donation or loss of 1 pint of blood within 3 months, or donation of plasma within 7 days prior to first dose of study medication or had a transfusion of any blood product within 3 months prior to study drug administration.
27. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g per day acetaminophen and HRT/hormonal contraception) within the last 30 days or five half-lives (whichever is longer), before IMP administration. Exceptions may apply on a case-by-case basis, if considered not to interfere with the objectives of the study, as determined by the Investigator.
28. Subjects who have been administered a drug by depot injection within 30 days prior to the initial study drug administration or 6 half-lives of that drug, whichever is longer and at the discretion of the Investigator or who have received a recent (as determined by the Investigator) live or attenuated vaccination (with exception of a COVID-19 vaccine or flu vaccine), or exposure to communicable viral diseases such as chicken pox, varicella, and measles.
29. Failure to satisfy the Investigator of fitness to participate for any other reason.
30. Known hypersensitivity to egg, soy or peanut proteins.
31. Food allergies deemed clinically relevant by the investigator which would hinder ability to adhere to the prescribed diet.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB (Organic phosphate/ Inorganic phosphate); Period 1: Regimen A (Organic phosphate (sodium glycerophosphate SGP)); Period 2: Regimen B (Inorganic phosphate (Sodium Phosphates Injection NaP))	Drug: Sodium Glycerophosphate Injection; Organic phosphate (SGP) will be diluted with 500mL of sodium chloride (0.9% normal saline) to achieve an equimolar IV phosphate dose of 60 mmol over 4 hours (h); Drug: Sodium Phosphates Injection; Inorganic phosphate (NaP) will be diluted with 500mL of sodium chloride (0.9% normal saline) to achieve an equimolar IV phosphate dose of 60 mmol over 4 h
Experimental: Sequence BA (Inorganic phosphate/ Organic phosphate); Period 1: Regimen B (Inorganic phosphate (Sodium Phosphates Injection NaP)); Period 2: Regimen A (Organic phosphate (sodium glycerophosphate SGP))	Drug: Sodium Glycerophosphate Injection; Organic phosphate (SGP) will be diluted with 500mL of sodium chloride (0.9% normal saline) to achieve an equimolar IV phosphate dose of 60 mmol over 4 hours (h); Drug: Sodium Phosphates Injection; Inorganic phosphate (NaP) will be diluted with 500mL of sodium chloride (0.9% normal saline) to achieve an equimolar IV phosphate dose of 60 mmol over 4 h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline-corrected maximum observed concentration (C(maxbc)) for inorganic phosphate	Serum PK parameter	Days 1, 2, 7, and 8
Baseline-corrected area under the curve from time 0 to 24h post-dose (AUC(0-24bc)) for inorganic phosphate	Serum PK parameter	Days 1, 2, 7, and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline-corrected total urinary inorganic phosphate excreted in the urine (Ae(0-24bc))	Urine PK parameter	Days 1 and 7
Time of maximum observed concentration (T(max)) for inorganic phosphate	Serum PK parameter	Days 1, 2, 7, and 8
Apparent terminal elimination half-life (T(1/2 z)) for inorganic phosphate	Serum PK parameter	Days 1, 2, 7, and 8
Elimination rate constant (K(z)) for inorganic phosphate	Serum PK parameter	Days 1, 2, 7, and 8
Maximum observed concentration (C(max)) for inorganic phosphate	Serum PK parameter	Days 1, 2, 7, and 8
Area under the curve from time 0 to 24h post-dose (AUC(0-24)) for inorganic phosphate	Serum PK parameter	Days 1, 2, 7, and 8
Total urinary inorganic phosphate excreted in the urine (Ae(0-24))	Urine PK parameter	Days 1 and 7
Baseline-corrected time of maximum observed concentration (T(maxbc)) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
T(max) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
Baseline-corrected apparent terminal elimination half-life (T(1/2 zbc)) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
T(1/2 z) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
Baseline-corrected elimination rate constant (K(zbc)) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
K(z) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
C(maxbc) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
C(max) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
AUC(0-24bc) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
AUC(0-24) for glycerophosphate	Serum PK parameter	Days 1, 2, 7, and 8
T(maxbc) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
T(max) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
T(1/2 zbc) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
T(1/2 z) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
K(zbc) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
K(z) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
C(maxbc) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
C(max) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
AUC(0-24bc) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
AUC(0-24) for glycerol	Serum PK parameter	Days 1, 2, 7, and 8
Change from baseline in Alanine Aminotransferase (ALT)	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in Alkaline Phosphatase	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in Aspartate Aminotransferase (AST)	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in total bilirubin	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in direct bilirubin	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in eGFR	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in Blood Urea Nitrogen (BUN)	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in creatinine	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in calcium	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in phosphate	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in magnesium	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in potassium	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in sodium	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in respiratory rate	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in heart rate	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in temperature	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Change from baseline in blood pressure	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Number of subjects with any physical examination interpreted as abnormal	Safety outcome	Baseline through Day 11
Number of subjects experiencing any clinically significant abnormality in ECGs	Safety outcome	Baseline, Day 1, Day 2, Day 7, Day 8
Number of subjects experiencing adverse events	Safety outcome	Baseline through Day 20
Change from baseline in ionized calcium	Safety outcome	Day 1, Day 7
Number of subjects experiencing any clinically significant abnormality in telemetry	Safety outcome	Day 1, Day 7

Collaborators and Investigators

• Sponsor: Baxter Healthcare Corporation
• Investigators: Study Director: Erika Ryan, DCN, MS, RD, CDN, CNSC, Baxter Healthcare Corporation

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2025
• Primary Completion (Actual): May 22, 2025
• Study Completion (Actual): May 22, 2025

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: pharmacokinetic; intravenous; parenteral nutrition; inorganic phosphate; organic phosphate; sodium glycerophosphate
• Other Study ID Numbers: BXU561373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No