Parenteral Nutrition
Conditions
Keywords
organic phosphate, inorganic phosphate, sodium glycerophosphate, pharmacokinetic, intravenous, parenteral nutrition
Brief summary
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).
Interventions
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)
DRUGSodium 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
Sponsors
Baxter Healthcare Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-corrected maximum observed concentration (C(maxbc)) for inorganic phosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Baseline-corrected area under the curve from time 0 to 24h post-dose (AUC(0-24bc)) for inorganic phosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of maximum observed concentration (T(max)) for inorganic phosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Apparent terminal elimination half-life (T(1/2 z)) for inorganic phosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Elimination rate constant (K(z)) for inorganic phosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Maximum observed concentration (C(max)) for inorganic phosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Area under the curve from time 0 to 24h post-dose (AUC(0-24)) for inorganic phosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Baseline-corrected time of maximum observed concentration (T(maxbc)) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| T(max) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Baseline-corrected apparent terminal elimination half-life (T(1/2 zbc)) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| T(1/2 z) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| Baseline-corrected elimination rate constant (K(zbc)) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| K(z) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| C(maxbc) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| C(max) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| AUC(0-24bc) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| AUC(0-24) for glycerophosphate | Days 1, 2, 7, and 8 | Serum PK parameter |
| T(maxbc) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| T(max) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| T(1/2 zbc) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| T(1/2 z) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| K(zbc) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| K(z) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| C(maxbc) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| C(max) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| AUC(0-24bc) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| AUC(0-24) for glycerol | Days 1, 2, 7, and 8 | Serum PK parameter |
| Change from baseline in Alanine Aminotransferase (ALT) | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in Alkaline Phosphatase | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in Aspartate Aminotransferase (AST) | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in total bilirubin | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in direct bilirubin | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in eGFR | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in Blood Urea Nitrogen (BUN) | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in creatinine | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in calcium | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in phosphate | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in magnesium | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in potassium | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in sodium | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in ionized calcium | Day 1, Day 7 | Safety outcome |
| Change from baseline in respiratory rate | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in heart rate | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Change from baseline in temperature | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Total urinary inorganic phosphate excreted in the urine (Ae(0-24)) | Days 1 and 7 | Urine PK parameter |
| Number of subjects with any physical examination interpreted as abnormal | Baseline through Day 11 | Safety outcome |
| Number of subjects experiencing any clinically significant abnormality in telemetry | Day 1, Day 7 | Safety outcome |
| Number of subjects experiencing any clinically significant abnormality in ECGs | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Number of subjects experiencing adverse events | Baseline through Day 20 | Safety outcome |
| Change from baseline in blood pressure | Baseline, Day 1, Day 2, Day 7, Day 8 | Safety outcome |
| Baseline-corrected total urinary inorganic phosphate excreted in the urine (Ae(0-24bc)) | Days 1 and 7 | Urine PK parameter |
Countries
United States
Outcome results
None listed