Trial Outcomes & Findings for Clinical Evaluation of the Pharmacokinetic Goldenseal-Metformin Interaction in Diabetic Patients (NCT NCT05081583)
NCT ID: NCT05081583
Last Updated: 2024-12-19
Results Overview
Area under the plasma concentration time curve of metformin
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
22 participants
Primary outcome timeframe
Before and 20 minutes, 40 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours after midazolam administration.
Results posted on
2024-12-19
Participant Flow
A washout period of ≥7 days between each arm was implemented in the study design.
Participant milestones
| Measure |
Midazolam Alone - Washout - Midazolam + Acute Goldenseal - Washout - Midazolam + Chronic Goldenseal
Twenty-two adults (12 males, 10 females) with type 2 diabetes participated in this three-arm, crossover study to assess a pharmacokinetic natural product-drug interaction. In arm 1 (midazolam alone), participants were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter; at this time, participants were instructed to co-administer their entire daily dose of metformin orally. For Arm 2 (midazolam + acute goldenseal exposure), the same 22 participants were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. For Arm 3 (chronic goldenseal exposure), participants self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration for all 3 arms of the study. A washout period of 7 days separated each arm to ensure appropriate washout of midazolam. Participants continued their routine administration of metformin as prescribed throughout the duration of the study without interruption in pharmacotherapy.
Midazolam HCl 1mg/mL inj: 0.5 mL of intravenous solution
Goldenseal (Hydrastis canadensis) 550 mg capsules: dried root powder in vegetable capsules (Solaray; Lot #1020199)
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|---|---|
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Overall Study
STARTED
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22
|
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Overall Study
COMPLETED
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22
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Clinical Evaluation of the Pharmacokinetic Goldenseal-Metformin Interaction in Diabetic Patients
Baseline characteristics by cohort
| Measure |
Midazolam Alone - Washout - Midazolam + Acute Goldenseal - Washout - Midazolam + Chronic Goldenseal
n=22 Participants
Twenty-two adults (12 males, 10 females) with type 2 diabetes participated in this three-arm, crossover study to assess a pharmacokinetic natural product-drug interaction. In arm 1 (midazolam alone), participants were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter; at this time, participants were instructed to co-administer their entire daily dose of metformin orally. For Arm 2 (midazolam + acute goldenseal exposure), the same 22 participants were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. For Arm 3 (chronic goldenseal exposure), participants self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration for all 3 arms of the study. A washout period of 7 days separated each arm to ensure appropriate washout of midazolam. Participants continued their routine administration of metformin as prescribed throughout the duration of the study without interruption in pharmacotherapy.
Midazolam HCl 1mg/mL inj: 0.5 mL of intravenous solution
Goldenseal (Hydrastis canadensis) 550 mg capsules: dried root powder in vegetable capsules (Solaray; Lot #1020199)
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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22 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Sex: Female, Male
Female
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10 Participants
n=5 Participants
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Sex: Female, Male
Male
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12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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2 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
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1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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20 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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1 Participants
n=5 Participants
|
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Before and 20 minutes, 40 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours after midazolam administration.Population: All 22 participants completed the 3 arms of the study (baseline, acute goldenseal exposure, and chronic goldenseal exposure).
Area under the plasma concentration time curve of metformin
Outcome measures
| Measure |
Study Arm 1: Baseline
n=22 Participants
Twenty-two type 2 diabetic subjects (12 men, 10 women) were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter in conjunction with their daily oral administration of metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration. Participants self-administered their metformin as prescribed throughout the entirety of the study without interruption in pharmacotherapy.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
|
Study Arm 2: Acute Goldenseal Exposure
n=22 Participants
For Arm 2, the same 22 subjects were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1. With respect to midazolam administration, a washout period of 7 days separated Arm 2 from Arm 1.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
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Study Arm 3: Chronic Goldenseal Exposure
n=22 Participants
For Arm 3, the same 22 subjects self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1 and 2. A designated washout period for midazolam was not necessary to separate Arm 3 since there will be 27 days of goldenseal administration prior to the midazolam administration.
Midazolam HCl 1mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): Goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
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Metformin AUC
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59.6 mcg*hr/mL
Interval 52.0 to 68.5
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54.5 mcg*hr/mL
Interval 48.2 to 61.7
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57.3 mcg*hr/mL
Interval 50.3 to 65.3
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PRIMARY outcome
Timeframe: Before and 20 minutes, 40 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours after midazolam administration.maximum concentration of metformin
Outcome measures
| Measure |
Study Arm 1: Baseline
n=22 Participants
Twenty-two type 2 diabetic subjects (12 men, 10 women) were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter in conjunction with their daily oral administration of metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration. Participants self-administered their metformin as prescribed throughout the entirety of the study without interruption in pharmacotherapy.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
|
Study Arm 2: Acute Goldenseal Exposure
n=22 Participants
For Arm 2, the same 22 subjects were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1. With respect to midazolam administration, a washout period of 7 days separated Arm 2 from Arm 1.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
|
Study Arm 3: Chronic Goldenseal Exposure
n=22 Participants
For Arm 3, the same 22 subjects self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1 and 2. A designated washout period for midazolam was not necessary to separate Arm 3 since there will be 27 days of goldenseal administration prior to the midazolam administration.
Midazolam HCl 1mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): Goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
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Metformin Cmax
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8.92 nM
Interval 7.86 to 10.1
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8.36 nM
Interval 7.55 to 9.27
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8.26 nM
Interval 7.37 to 9.25
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SECONDARY outcome
Timeframe: 0-24hhalf-life of metformin
Outcome measures
| Measure |
Study Arm 1: Baseline
n=22 Participants
Twenty-two type 2 diabetic subjects (12 men, 10 women) were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter in conjunction with their daily oral administration of metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration. Participants self-administered their metformin as prescribed throughout the entirety of the study without interruption in pharmacotherapy.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
|
Study Arm 2: Acute Goldenseal Exposure
n=22 Participants
For Arm 2, the same 22 subjects were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1. With respect to midazolam administration, a washout period of 7 days separated Arm 2 from Arm 1.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
|
Study Arm 3: Chronic Goldenseal Exposure
n=22 Participants
For Arm 3, the same 22 subjects self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1 and 2. A designated washout period for midazolam was not necessary to separate Arm 3 since there will be 27 days of goldenseal administration prior to the midazolam administration.
Midazolam HCl 1mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): Goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
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Metformin Half-Life
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4.73 hours
Interval 4.18 to 5.35
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4.70 hours
Interval 4.22 to 5.23
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4.79 hours
Interval 4.27 to 5.37
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SECONDARY outcome
Timeframe: 0-24hrenal clearance of metformin
Outcome measures
| Measure |
Study Arm 1: Baseline
n=22 Participants
Twenty-two type 2 diabetic subjects (12 men, 10 women) were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter in conjunction with their daily oral administration of metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration. Participants self-administered their metformin as prescribed throughout the entirety of the study without interruption in pharmacotherapy.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
|
Study Arm 2: Acute Goldenseal Exposure
n=22 Participants
For Arm 2, the same 22 subjects were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1. With respect to midazolam administration, a washout period of 7 days separated Arm 2 from Arm 1.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
|
Study Arm 3: Chronic Goldenseal Exposure
n=22 Participants
For Arm 3, the same 22 subjects self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1 and 2. A designated washout period for midazolam was not necessary to separate Arm 3 since there will be 27 days of goldenseal administration prior to the midazolam administration.
Midazolam HCl 1mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): Goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
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Metformin Renal Clearance
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259 mL / min
Interval 203.0 to 331.0
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249 mL / min
Interval 200.0 to 309.0
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250 mL / min
Interval 199.0 to 314.0
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SECONDARY outcome
Timeframe: Before and 20 minutes, 40 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours after midazolam administration.area under the concentration vs. time curve of midazolam
Outcome measures
| Measure |
Study Arm 1: Baseline
n=22 Participants
Twenty-two type 2 diabetic subjects (12 men, 10 women) were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter in conjunction with their daily oral administration of metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration. Participants self-administered their metformin as prescribed throughout the entirety of the study without interruption in pharmacotherapy.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
|
Study Arm 2: Acute Goldenseal Exposure
n=22 Participants
For Arm 2, the same 22 subjects were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1. With respect to midazolam administration, a washout period of 7 days separated Arm 2 from Arm 1.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
|
Study Arm 3: Chronic Goldenseal Exposure
n=22 Participants
For Arm 3, the same 22 subjects self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1 and 2. A designated washout period for midazolam was not necessary to separate Arm 3 since there will be 27 days of goldenseal administration prior to the midazolam administration.
Midazolam HCl 1mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): Goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
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|---|---|---|---|
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Midazolam AUC
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31.9 mcg*hr/mL
Interval 27.1 to 37.7
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31.1 mcg*hr/mL
Interval 26.4 to 36.5
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29.7 mcg*hr/mL
Interval 25.7 to 34.3
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Adverse Events
Study Arm 1: Baseline
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Study Arm 2: Acute Goldenseal Exposure
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Study Arm 3: Chronic Goldenseal Exposure
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Study Arm 1: Baseline
n=22 participants at risk
Twenty-two type 2 diabetic subjects (12 men, 10 women) were administered a single dose of midazolam (0.5 mg) intravenously via a peripherally inserted catheter in conjunction with their daily oral administration of metformin. Plasma and urine were collected from 0-24 hours post-midazolam administration. Participants self-administered their metformin as prescribed throughout the entirety of the study without interruption in pharmacotherapy.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
|
Study Arm 2: Acute Goldenseal Exposure
n=22 participants at risk
For Arm 2, the same 22 subjects were administered a single dose of goldenseal (3.3 g) orally 30 minutes prior to administration of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1. With respect to midazolam administration, a washout period of 7 days separated Arm 2 from Arm 1.
Midazolam HCl 1 mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
|
Study Arm 3: Chronic Goldenseal Exposure
n=22 participants at risk
For Arm 3, the same 22 subjects self-administered goldenseal (1.1 g) orally three times daily for 27 days. On the 28th day, participants were administered the goldenseal three times daily, as well as the single dose of midazolam and metformin. Plasma and urine were collected in a manner identical to that in Arm 1 and 2. A designated washout period for midazolam was not necessary to separate Arm 3 since there will be 27 days of goldenseal administration prior to the midazolam administration.
Midazolam HCl 1mg/mL inj: 0.5 mL of an intravenous solution was administered.
Goldenseal (Hydrastis canadensis): Goldenseal (Solaray; Lot #1020199) was supplied as dried root powder in vegetable capsules, each containing 550 mg of herbal content. Goldenseal capsules were administered with 240 mL of water.
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|---|---|---|---|
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Nervous system disorders
presyncope
|
40.9%
9/22 • All participants were monitored up to whenever they completed the final arm of the study, which was on average ~2 months.
|
9.1%
2/22 • All participants were monitored up to whenever they completed the final arm of the study, which was on average ~2 months.
|
9.1%
2/22 • All participants were monitored up to whenever they completed the final arm of the study, which was on average ~2 months.
|
|
Nervous system disorders
emesis
|
0.00%
0/22 • All participants were monitored up to whenever they completed the final arm of the study, which was on average ~2 months.
|
9.1%
2/22 • All participants were monitored up to whenever they completed the final arm of the study, which was on average ~2 months.
|
0.00%
0/22 • All participants were monitored up to whenever they completed the final arm of the study, which was on average ~2 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place