Effect of VI-0521 (Qsymia®) on Glomerular Filtration Rate (GFR) in Overweight or Obese Healthy Subjects

• Sponsor: VIVUS LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02229214
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arms: 2
• Actual Duration (Months): 3
• Patients Per Site Per Month: 16.9

Study Details

Study Description

Brief Summary

The main purpose of this study is measure the effect of VI-0521 on kidney function. Specifically, glomerular filtration rate (GFR) will be measured at baseline, after 4 weeks of study treatment, and after an additional 4 weeks of off-treatment recovery.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Qsymia; Drug: Placebo	Phase 4

Detailed Description

This is a randomized, double-blind, placebo-controlled, single-site study in healthy overweight or obese male and female volunteers. Oral VI-0521 (combination of phentermine and topiramate [PHEN/TPM] extended-release capsule) will be administered daily as follows:

• Days 1-3: PHEN/TPM 3.75 mg /23 mg

• Days 4-6: PHEN/TPM 7.5 mg /46 mg

• Days 7-9: PHEN/TPM 11.25 mg /69 mg

• Days 10-28: PHEN/TPM 15 mg /92 mg

A single dose of Iohexol (a non-radioactive iodine-containing contrast agent) will be administered intravenously on three separate occasions.

The study will include a total of 50 healthy subjects (40 active and 10 placebo), all of whom will have overnight stays on 3 separate occasions.

Total study duration is approximately 10 weeks (2 weeks screening, 4 weeks study treatment, 4 weeks post treatment follow up).

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Effect of VI-0521 on the Glomerular Filtration Rate of Healthy Overweight or Obese Subjects
• Actual Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VI-0521 (Qsymia) Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg)	Drug: Qsymia; Other Names: VI-0521 Phentermine and Topiramate ER (Extended Release)
Placebo Comparator: Sugar pill Days 1-28: Placebo	Drug: Placebo; Other Names: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to End of Treatment [Baseline, end of treatment]

   Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR.

2. Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to 28 Days After End of Treatment [Baseline, 28 days after end of treatment]

   Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR

Secondary Outcome Measures

1. Change in Serum Creatinine From Baseline to End of Treatment [Baseline, end of treatment]

2. Change in Serum Creatinine From Baseline to 28 Days After End of Treatment [Baseline, 28 days after end of treatment]

3. Change in Cystatin C From Baseline to End of Treatment [Baseline, end of treatment]

4. Change in Cystatin C From Baseline to 28 Days After End of Treatment [Baseline, 28 days after end of treatment]

5. Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to End of Treatment [Baseline, end of treatment]

6. Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to 28 Days After End of Treatment [Baseline, 28 days after end of treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Key Inclusion Criteria:

• Male or female 18 - 65 years of age, medically healthy with no clinically significant screening abnormalities

• BMI of ≥27 to ≤45 kg/m2

• No use of any medication (prescription, over the counter (OTC) or herbal preparations) with the exception of contraception for the entirety of the study

Key Exclusion Criteria:

• Allergy or hypersensitivity to radio contrast media, iodine or shellfish

• Plans to significantly alter their diet through fasting, very low caloric intake, elimination of certain foods (gluten, milk, meat, etc.) or similar

• Plans to undertake a significant change to physical exercise levels (i.e., initiate training for a marathon) during the study period

• Consumption of a high protein diet or protein/body building meal supplementation and/or replacement. The use of any product containing creatine is strictly prohibited

• History of glaucoma or increased intraocular pressure

• History of bipolar disorder or psychosis, history of psychiatric hospitalization, greater than one lifetime episode of major depression, current depression of moderate or greater severity, presence or history of suicidal behavior or ideation with some intent to act on it

• Cholelithiasis (gallstones) within the past 6 months

• History of nephrolithiasis (kidney stones)

• Evidence of any clinically significant renal, pulmonary, hepatic, psychiatric or other condition by history, physical examination or laboratory studies that, in the opinion of the investigator, would contraindicate the administration of study medications, affect compliance, interfere with study evaluations or confound the interpretation of study results as determined by the investigator

• Current use of any tobacco products including cigarettes, cigars, pipes, and chewing tobacco, or nicotine replacement products (e.g., patch, gum, lozenge, etc.), or chronic use within the previous three months prior to screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Center	Lakewood	Colorado	United States	80228

Sponsors and Collaborators

• VIVUS LLC

Investigators

• Principal Investigator: Chris Galloway, MD,

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT02229214
• Other Study ID Numbers: OB-404
• First Posted: Sep 1, 2014
• Last Update Posted: Nov 7, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by VIVUS LLC: Renal function; Glomerular Filtration Rate; Kidney function; Qsymia; Iohexol; Serum Creatinine; Creatinine clearance; Renal Clearance; VI-0521; Healthy volunteers
• Additional relevant MeSH terms: Overweight; Topiramate; Phentermine

Study Results

Participant Flow

Arm/Group Title	VI-0521 (Qsymia)	Placebo
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Sugar Pill
Period Title: Overall Study
STARTED	41	10
COMPLETED	35	10
NOT COMPLETED	6	0

Baseline Characteristics

Arm/Group Title	VI-0521 (Qsymia)	Placebo	Total
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Placebo (sugar pill)	Total of all reporting groups
Overall Participants	41	10	51
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.4 (11.07)	37.6 (9.80)	38.2 (10.74)
Sex: Female, Male (Count of Participants)
Female	27 65.9%	4 40%	31 60.8%
Male	14 34.1%	6 60%	20 39.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 31.7%	3 30%	16 31.4%
Not Hispanic or Latino	28 68.3%	7 70%	35 68.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 4.9%	0 0%	2 3.9%
Asian	1 2.4%	0 0%	1 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 7.3%	1 10%	4 7.8%
White	30 73.2%	8 80%	38 74.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 12.2%	1 10%	6 11.8%
Region of Enrollment (participants) [Number]
United States	41 100%	10 100%	51 100%
BMI (Kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg/m^2]	33.2 (4.72)	31.3 (2.81)	32.8 (4.46)
iGFR (mL/min/1.73m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73m^2]	95.1 (14.05)	87.3 (9.06)	93.6 (13.49)

Outcome Measures

1. Primary Outcome

Title	Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to End of Treatment
Description	Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR.
Time Frame	Baseline, end of treatment

Outcome Measure Data

Analysis Population Description

The number analyzed in this outcome measure are those subjects who have both baseline and end of treatment iGFR measurements.

Arm/Group Title	VI-0521 (Qsymia)	Placebo
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Sugar Pill
Measure Participants	34	10
Mean (Standard Error) [mL/min/1.73 m^2]	-14.92 (1.28)	1.08 (2.28)

2. Secondary Outcome

Title	Change in Serum Creatinine From Baseline to End of Treatment
Time Frame	Baseline, end of treatment

Outcome Measure Data

Analysis Population Description

The number analyzed in this outcome measure are those subjects who have both baseline and end of treatment serum creatininine measurements

Arm/Group Title	VI-0521 (Qsymia)	Sugar Pill
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Placebo
Measure Participants	35	10
Mean (Standard Error) [mg/dL]	0.10 (0.01)	0.03 (0.03)

3. Secondary Outcome

Title	Change in Serum Creatinine From Baseline to 28 Days After End of Treatment
Time Frame	Baseline, 28 days after end of treatment

Outcome Measure Data

Analysis Population Description

The number analyzed in this outcome measure are those subjects who have both baseline and 28 days after end of treatment serum creatinine measurements.

Arm/Group Title	VI-0521 (Qsymia)	Sugar Pill
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Placebo
Measure Participants	35	10
Mean (Standard Error) [mg/dL]	-0.01 (0.01)	0.03 (0.02)

4. Secondary Outcome

Title	Change in Cystatin C From Baseline to End of Treatment
Time Frame	Baseline, end of treatment

Outcome Measure Data

Analysis Population Description

The number analyzed in this outcome measure are those subjects who have both baseline and end of treatment cystatin C measurements.

Arm/Group Title	VI-0521 (Qsymia)	Placebo
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Sugar Pill
Measure Participants	35	10
Mean (Standard Error) [mg/L]	0.04 (0.01)	0.03 (0.02)

5. Primary Outcome

Title	Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to 28 Days After End of Treatment
Description	Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR
Time Frame	Baseline, 28 days after end of treatment

Outcome Measure Data

Analysis Population Description

The number analyzed in this outcome measure are those subjects who have both baseline and 28 days after treatment iGFR measurements.

Arm/Group Title	VI-0521 (Qsymia)	Sugar Pill
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Placebo
Measure Participants	32	10
Mean (Standard Error) [mL/min/1.73 m^2]	-3.75 (1.49)	2.34 (1.34)

6. Secondary Outcome

Title	Change in Cystatin C From Baseline to 28 Days After End of Treatment
Time Frame	Baseline, 28 days after end of treatment

Outcome Measure Data

Analysis Population Description

The number analyzed in this outcome measure are those subjects who have both baseline and 28 days after end of treatment cystatin C measurements.

Arm/Group Title	VI-0521 (Qsymia)	Placebo
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Sugar Pill
Measure Participants	35	10
Mean (Standard Error) [mg/L]	0.01 (0.01)	0.02 (0.01)

7. Secondary Outcome

Title	Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to End of Treatment
Time Frame	Baseline, end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VI-0521 (Qsymia)	Placebo
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Placebo (sugar pill)
Measure Participants	41	10
Number [percent of participants]	48.8 119%	0 0%

8. Secondary Outcome

Title	Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to 28 Days After End of Treatment
Time Frame	Baseline, 28 days after end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VI-0521 (Qsymia)	Placebo
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia	Days 1-28: Placebo Placebo (sugar pill)
Measure Participants	41	10
Number [percent of participants]	7.3 17.8%	0 0%

Adverse Events

Time Frame	3 months
Arm/Group Title	VI-0521 (Qsymia)		Placebo
Arm/Group Description	Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) Qsymia		Days 1-28: Placebo Sugar Pill
All Cause Mortality
	VI-0521 (Qsymia)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	VI-0521 (Qsymia)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		0/10 (0%)
Injury, poisoning and procedural complications
Fall	1/41 (2.4%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	VI-0521 (Qsymia)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/41 (80.5%)		6/10 (60%)
Eye disorders
Ocular Hyperaemia	0/41 (0%)		1/10 (10%)
Gastrointestinal disorders
Dry mouth	5/41 (12.2%)		0/10 (0%)
Nausea	4/41 (9.8%)		1/10 (10%)
Paraesthesia Oral	3/41 (7.3%)		0/10 (0%)
Injury, poisoning and procedural complications
Excoriation	0/41 (0%)		2/10 (20%)
Fall	0/41 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Decreased Appetite	4/41 (9.8%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/41 (2.4%)		1/10 (10%)
Arthralgia	0/41 (0%)		1/10 (10%)
Muscle Spasms	0/41 (0%)		1/10 (10%)
Musculoskeletal Pain	0/41 (0%)		1/10 (10%)
Nervous system disorders
Paraesthesia	12/41 (29.3%)		0/10 (0%)
Headache	9/41 (22%)		2/10 (20%)
Dizziness	7/41 (17.1%)		0/10 (0%)
Psychiatric disorders
Insomnia	5/41 (12.2%)		0/10 (0%)
Reproductive system and breast disorders
Dysfunctional Uterine Bleeding	1/41 (2.4%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	2/41 (4.9%)		1/10 (10%)
Sinus Congestion	0/41 (0%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.