The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE

NeuroTherapia, Inc.

Status and phase: Completed; Phase 2

Conditions: Chronic Kidney Disease

Treatments: Drug: Placebo (for lanthanum carbonate); Drug: Placebo (for Nicotinamide); Drug: Nicotinamide; Drug: Lanthanum Carbonate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02258074

DK099877-C

U01DK099877 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients with Chronic Kidney Disease (CKD) stages 3-4.

Enrollment: 205 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2
2. Age 18-85 years
3. Serum phosphate ≥ 2.8 mg/dL
4. Platelet count ≥ 125,000/mm3
5. Able to provide consent
6. Able to travel to study visits
7. Able to eat at least two meals a day
8. In the opinion of the site investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.

Exclusion criteria

1. History of allergic reaction to nicotinamide, niacin (excluding flushing), multivitamin preparations, or lanthanum carbonate

2. Liver disease, defined as known cirrhosis by imaging or physician diagnosis, documented alcohol use > 14 drinks/week, or aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin concentrations > 2 times the upper limit of the local laboratory reference range

3. Creatine kinase (CK) concentrations > 2 times the upper limit of the local laboratory reference range

4. Major hemorrhagic event within the past six months requiring in-patient admission

5. Blood or platelet transfusion within the past six months

6. Secondary hyperparathyroidism (PTH > 5 times the upper limit of normal range for the laboratory) or currently taking cinacalcet (Sensipar)

7. Current, clinically significant malabsorption, as determined at the discretion of the site investigator

8. Anemia (screening Hg < 9.0 g/dl)

9. Serum albumin < 2.5 mg/dl

10. Anticipated initiation of dialysis or kidney transplantation within 12 months as assessed by and at the discretion of the site investigator.

11. Use of immunosuppressive medications (stable oral steroids ≤ 10 mg of prednisone/day or inhaled steroids are exempted)

12. In the opinion of the site investigator, active abuse of alcohol or drugs

13. Recent (within the last 14 days) initiation or change in dose of treatment with 1,25 (OH)2 vitamin D or active vitamin D analogues (paricalcitol or hectorol). Patients on stable doses of these agents initiated more than 14 days prior to screening are eligible to participate.

14. Current or recent treatment (within the last 14 days) with phosphate binder or niacin/nicotinamide > 100 mg/day

15. Current participation in another clinical trial or other interventional research

16. Currently taking investigational drugs

17. Institutionalized individuals, including prisoners and nursing home residents

18. Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and localized prostate cancer are exempted)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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205 participants in 4 patient groups, including a placebo group

Lanthanum carbonate + nicotinamide

Experimental group

Description:

One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.

Treatment:

Drug: Nicotinamide

Drug: Lanthanum Carbonate

Lanthanum carbonate + nicotinamide placebo

Placebo Comparator group

Description:

Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.

Treatment:

Drug: Placebo (for Nicotinamide)

Drug: Lanthanum Carbonate

Lanthanum carbonate placebo and nicotinamide

Active Comparator group

Description:

One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.

Treatment:

Drug: Placebo (for lanthanum carbonate)

Drug: Nicotinamide

Lanthanum carbonate placebo and nicotinamide placebo

Placebo Comparator group

Description:

One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.

Treatment:

Drug: Placebo (for lanthanum carbonate)

Drug: Placebo (for Nicotinamide)