A Study to Evaluate the Effect of Two Fixed-Dose Leucine, Sildenafil and Metformin Combinations on Blood Pressure in Individuals With Hypertension

NCT07647003 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: IND 1687261R44HL182451-01
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

This 12-week, randomized, double-blind, placebo-controlled Phase 2 study will evaluate two fixed-dose oral combinations of L-leucine, sildenafil, and metformin (NS-0200) versus matching placebo in adults 18-75 years with hypertension. Approximately 150 subjects will be screened to randomize \~150 (≈50 per arm) with an expected completer population of \~120. The primary objective is to compare change in mean seated systolic blood pressure from baseline (Day 1) to Week 12 (Day 84) for each NS-0200 dose versus placebo. Secondary outcomes include change in seated diastolic blood pressure and change in body weight. Safety will be monitored through adverse events, labs, vital signs, ECGs, and pregnancy testing.

Conditions

Hypertension

Keywords

Hypertension; High blood pressure; NS-0200; Leucine; Sildenafil; Metformin; Blood pressure; Randomized; Placebo

Outcome Measures

Primary Outcomes (1)

• Change in systolic blood pressure compared to placebo from baseline to study termination

  Systolic blood pressure will be measured in all subjects at visits 1 through 5 or at early termination. BP will be taken using a standardized automated cuff-based instrument (Omron HEM-907XL or equivalent). Qualified site personnel will program the machine to capture a series of 3 measurements of SBP starting with a 5-minute delay for the first reading followed by a delay of 2 minutes between the subsequent readings.

  From baseline to study completion, approximately 12 weeks

Secondary Outcomes (2)

• Change in diastolic blood pressure compared to placebo from baseline to study termination

  From baseline to study completion, approximately 12 weeks

• Change in body weight, from baseline to study termination

  From baseline to study completion, approximately 12 weeks

Other Outcomes (4)

• Change in waist circumference from baseline to study termination

  From baseline to study completion, approximately 12 weeks

• Change in lipid profile from baseline to study termination

  From baseline to study completion, approximately 12 weeks

• Change in fasting glucose from baseline to study termination

  From baseline to study completion, approximately 12 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

3 tablets/dose orally BID (30 min before meals)

Other: Placebo

NS-0200 (low sildenafil)

EXPERIMENTAL

two tablets 550 mg L-leucine + 250 mg metformin and one tablet 1.0 mg sildenafil per dose; 3 tablets/dose orally BID

Drug: NS-0200 (low sildenafil)

NS-0200 (higher sildenafil)

EXPERIMENTAL

two tablets 550 mg L-leucine + 250 mg metformin and one tablet 4.0 mg sildenafil per dose; 3 tablets/dose orally BID

Drug: NS-0200 (higher sildenafil)

Interventions

Placebo OTHER

9.5% microcrystalline cellulose PH 102, 5.0% crospovidone XL 10, 1.0% silica gel (Syloid 244), 0.5% magnesium stearate I MF3V for the leucine-matched placebo; 99.5% Avicel PH200, 0.5% magnesium stearate (w/w) and Opadry II White coating 3% weight gain for the sildenafil matched placebo, self-administered by the patient as 3 tablets taken orally bid within 30 minutes prior to the morning and evening meal

Placebo

NS-0200 (low sildenafil) DRUG

Two tablets 550 mg L-leucine + 250 mg metformin and one tablet 1.0 mg sildenafil per dose; 3 tablets/dose orally BID

Also known as: TRIPLN (low sildenafil), TRIPLN

NS-0200 (low sildenafil)

NS-0200 (higher sildenafil) DRUG

Two tablets 550 mg L-leucine + 250 mg metformin and one tablet 4.0 mg sildenafil per dose; 3 tablets/dose orally BID

Also known as: TRIPLN (higher sildenafil), TRIPLN

NS-0200 (higher sildenafil)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤75 at study entry.
• Is male, or female and, if female, meets all of the following criteria: (1) Not breastfeeding; (2) Post-menopausal or negative serum pregnancy test result (human chorionic gonadotropin, beta subunit \[β- hCG\]) at screening (not required for hysterectomized females); (3) If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods \[male condom with spermicide, with or without cervical cap or diaphragm\], implants, injectables, oral contraceptives \[must have been using for at least the last 3 months\], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized or same sex partner) during the entire duration of the study Stable body weight (±5%) and health over the last 3 months.
• Systolic pressure \> 130 mm Hg
• Not on antihypertensive therapy for the preceding 30 days or on a stable dose over the 30 days preceding study entry of 1 or 2 antihypertensive agents.
• HbA1c \<9%.
• If on insulin, must be on a stable regimen for 3 months preceding study entry.
• If on GLP-1 agonist, must be on a stable regimen for 9 months with a stable total body weight for the preceding 3 months.
• Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal or not clinically significant.
• Is able to read, understand, and sign the informed consent forms (ICF) and, when applicable, an authorization to use and disclose protected health information form (consistent with Health Insurance Portability and Accountability Act of 1996 \[HIPAA\] legislation), communicate with the investigator, and understand and comply with protocol requirements.

You may not qualify if:

• \<18 or \>75 years of age
• On \>2 antihypertensive agent drug products
• Systolic pressure \>160 mm Hg
• Diastolic pressure \>110 mm Hg
• HbA1c \>9% at screening
• Severe renal impairment (eGFR \< 45 mg/mL/1.73 m2) and/or patients with acute or chronic metabolic acidosis (acidosis defined as \>25mmol/L computed without K).
• Use of any of the following medications in the eight weeks prior to entering screening for study participation and during the study: (1) Use of any anti-diabetes medication including metformin and any combination drug that contains metformin; (2) Sildenafil; (3) Tadalafil; (4) Vardenafil; (5) OCT2/MATE inhibitors (e.g. cimetidine, quinidine, and pyrimethamine); (6) Riociguat (guanylate cyclase stimulant); (7) Alpha blockers; (8) Nitrates (e.g. oral nitrates, sublingual nitroglycerine and nitroglycerine patches); (9) Potent CYP3A4 inhibitors (e.g., clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir)
• ≥ 5% weight change in the last 3 months
• Diseases interfering with metabolism (including metabolism of branched chain amino acids) and/or ingestive behavior (myxedema, Cushings disease, diabetes, schizophrenia, major psychoses, maple syrup urine disease, unmanaged depression etc.)
• History of alcohol abuse (defined ≥ 21 drinks per week for males and \> 14 drinks per week for females), within the past 3 months or failure on urinary drug screen
• History of substance abuse (including alcohol abuse as defined above) in the past 12 months or a positive screen for drugs (opioids without a prescription) of abuse or alcohol at screening
• Has received any investigational drug within 3 months of screening
• Has donated blood within 3 months before screening or is planning to donate blood during the study (due to HbA1c reading at screening)
• Other medical conditions that may diminish life expectancy to \<2 years, including known cancers
• Have been diagnosed with metastatic carcinomas in the last 5 years

Sponsors & Collaborators

• NuSirt Biopharma: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: June 15, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): May 2, 2027
• Study Completion (Estimated): July 7, 2027
• Last Updated: June 15, 2026

Record last verified: 2026-06