Type 2 DiabetesPhase 2Synergy104NCT00995345

Safety and Efficacy of Once-Daily KRP-104 in Type 2 Diabetics With Inadequate Glycemic Control on Metformin Alone

A Phase 2 study testing KRP-104 in people with Type 2 Diabetes, run by ActivX Biosciences, Inc. at 45 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to assess the safety and effectiveness of KRP-104 on glycemic control in patients with type 2 diabetes inadequately controlled on metformin alone. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Type 2 Diabetes
What is being tested?: KRP-104
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 403 participants
Where: 45 sitesin 7 countries
Study dates: Oct 2009to Jan 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients meeting the following criteria at the screening visit (Visit 1) will be eligible to participate in the trial:
Signed written informed consent;
Males and females 18 to 75 years of age, inclusive;
Females of childbearing potential must agree to use 2 adequate forms of barrier method contraception (eg, latex condom AND intrauterine device or a diaphragm) to avoid pregnancy while in the study;
On a stable dose (Greater than or equal to 10 weeks at the same dose) of metformin monotherapy (Less than or equal to 1500 mg/day or maximum tolerated dose), have an HbA1c greater than or equal to 7.0% and less than or equal to 10.5%; or
On metformin (less than or equal to 1500 mg/day) and 1 other antidiabetic agent (excluding TZD, insulin, or incretin therapies [DPP-4 inhibitors and GLP-1 analogues]) and have an HbA1c greater than or equal to 6.8% and less than or equal to 10.0%; or
Not on antidiabetic therapy (for at least 3 months prior to Visit 1) or have not been on a stable dose of metformin monotherapy for 10 weeks and have an HbA1c greater than or equal to 8.0% and less than or equal to 11.0%.

Who cannot join

History of type 1 diabetes mellitus or history of diabetic ketoacidosis or persistent hypoglycemia;
History or presence of alcoholism or drug abuse within the 2 years prior to dosing;
Typical consumption of greater than or equal to 10 drinks of alcohol weekly;
Presence of any of the following conditions:
Significant renal impairment (glomerular filtration rate less than 60 mL/min);
Diabetic gastroparesis;

Show all 17Show fewer

Active liver disease (other than asymptomatic nonalcoholic fatty liver disease), cirrhosis, or symptomatic gallbladder disease;
Fasting plasma glucose/blood glucose greater than 240 mg/dL (13.3 mmol/L) at Visit 3 (Week -2) (1 laboratory retest permitted);
Body mass index less than or equal to 20 kg/m2 and greater than or equal to 48 kg/m2;
Systolic blood pressure <100 mmHg or >160 mmHg and diastolic blood pressure <50 mmHg or >100 mmHg at Visit 3 (Note: medication to control blood pressure is allowed and should be optimized and stabilized prior to Visit 3);
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 X the upper limit of normal (ULN) (1 laboratory retest permitted);
Creatine phosphokinase (CPK) greater than 2 X the ULN (if not explained by muscular trauma or exercise) (1 laboratory retest permitted);
Serum creatinine >1.5 mg/dL for males (132.6 μmol/L) and 1.4 mg/dL for females (123.8 μmol/L);
Fasting triglycerides (TG) >600 mg/dL (6.78 mmol/L) at Visit 3 (Week -2) (Note: diet/exercise and lipid-lowering medication to control elevated TG is allowed; medications should be optimized and stabilized prior to Visit 3);
Treatment with pioglitazone or rosiglitazone within the previous 10 weeks (Visit 1); treatment with incretin therapy (DPP-4 inhibitors or GLP-1 analogues) within the previous 4 weeks (Visit 1);
Treatment with any type of insulin (ie, injected or inhaled) within the previous 3 months;
Must meet other laboratory and Medical History clinical criteria. Please contact recruitment center for referrals

Trial locations and contacts

45 sites in 7 countries.

Country

City, postcode or hospital

45 sites in 7 countries

United States17 sites

Study site
Austin, Texas
Study site
Beaver, Pennsylvania
Study site
Birmingham, Alabama
Study site
Cincinnati, Ohio
Study site
Delaware, Ohio
Study site
Greer, South Carolina
Study site
Honolulu, Hawaii
Study site
Houston, Texas
Study site
Jenkintown, Pennsylvania
Study site
Los Angeles, California
Study site
Marion, Ohio
Study site
Phoenix, Arizona
Study site
San Antonio, Texas
Study site
Sandy City, Utah
Study site
Valley Village, California
Study site
West Jordan, Utah
Study site
Winston-Salem, North Carolina

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South Africa8 sites

Study site
Bloemfontein, Free State
Study site
Cape Town, Western Cape
Study site
Durban, Kwazula-Natal
Study site
Johannesburg, Gauteng
Study site
Paarl, Western Cape
Study site
Port Elizabeth, Eastern Cape
Study site
Somerset West, Western Cape
Study site
Soweto, Gauteng

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Poland6 sites

Study site
Bialystok
Study site
Gdansk
Study site
Krakow
Study site
Lodz
Study site
Warsaw
Study site
Wroclaw

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Czechia5 sites

Study site
Chrudim III
Study site
Holešov
Study site
Mělník
Study site
Ostrava
Study site
Prague

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Russia5 sites

Study site
Arkhangelsk
Study site
Kemerovo
Study site
Moscow
Study site
Novosibirsk
Study site
Saint Petersburg

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Argentina3 sites

Study site
Buenos Aires
Study site
Córdoba
Study site
Loma Hermos Buenos Aires

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Guatemala1 site

Study site
Guatemala City

Other trials in Guatemala

About this study

Official title: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Asses the Safety and Efficacy of Once-Daily KRP-104 in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Metformin Alone.

The purpose of this study is to assess the safety and effectiveness of KRP-104 on glycemic control in patients with type 2 diabetes inadequately controlled on metformin alone.

Conditions: Type 2 Diabetes
Being tested: KRP-104, Placebo
Keywords: Type 2 Diabetes, Metformin
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KRP-104Drug
Tablet
PlaceboDrug
Tablet

Study groups in NCT00995345
Study group	Role	What they receive
Dose 1: KRP-104 40 mg	Experimental	Tablet, once-daily for 24 weeks Receives: Drug: KRP-104
Dose 2: KRP-104 80 mg	Experimental	Tablet, once-daily for 24 weeks Receives: Drug: KRP-104
Dose 3: KRP-104 100 mg	Experimental	Tablet, once-daily for 24 weeks Receives: Drug: KRP-104
Dose 4: KRP-104 20/120mg	Experimental	Tablet, once-daily for 24 weeks (dose switch from 20 to 120 mg at week 12) Receives: Drug: KRP-104
Placebo	Placebo comparator	Tablet, once-daily for 24 weeks Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in HbA1c From Baseline (Week 0) to Week 24
Mean Change in HbA1c (%) from Baseline to Week 24 with LOCF, ITT population LS mean (SE)
Measured: Week 24

Secondary outcomes (3)

Change in Body Weight
Mean Change in Body Weight (kg) from Baseline to Week 24 with LOCF- ITT
Measured: 24 weeks
Percentage of Patients Achieving HbA1c Less Than 7%
Subjects Achieving Target of Hemoglobin A1c <7.0% at Week 24 with LOCF - Intent-to-Treat Population
Measured: 24 weeks
Percentage of Patients Requiring Rescue Therapy for Elevated Glucose
Percentage of Subjects Requiring Rescue Therapy - Intent-to-Treat Population
Measured: 24 weeks of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2009Jan 2011

First posted15 Oct 2009 (estimated)
Study startOct 2009
Primary completionJan 2011
Study completionJan 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 403 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00995345
Sponsor's protocol ID: 0104-005
Acronym: Synergy104
Status last verified: Jun 2014
First submitted: 12 Oct 2009
Last updated: 26 Jun 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Plotkin DJ, Lewin A, Logan D, Kato T, Kozarich J, Wei X, Vest J, Orloff D. KRP-104, A Uniquely Prandial-Targeted DPP-4 Inhibitor. Abstract and Poster # 822, Presented at: European Association for the Study of Diabetes 38th Annual Meeting, Berlin Germany, October 1-5, 2012.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Asses the Safety and Efficacy of Once-Daily KRP-104 in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Metformin Alone.
ClinicalTrials.gov ID: NCT00995345
Acronym / sponsor ID: Synergy104 / 0104-005
Conditions: Type 2 Diabetes
Keywords: Type 2 Diabetes, Metformin
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 403 participants (actual)
Lead sponsor: ActivX Biosciences, Inc.Industry (pharma, biotech, devices)
Collaborators: Kyorin Pharmaceutical Co.,Ltd
Study start: Oct 2009
Primary completion: Jan 2011 (actual)
Study completion: Jan 2011 (actual)
First posted: 15 Oct 2009 (estimated)
Results: Posted 26 Jun 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to assess the safety and effectiveness of KRP-104 on glycemic control in patients with type 2 diabetes inadequately controlled on metformin alone.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Dose 1: KRP-104 40 mg	Experimental	Drug: KRP-104Tablet, once-daily for 24 weeks
Dose 2: KRP-104 80 mg	Experimental	Drug: KRP-104Tablet, once-daily for 24 weeks
Dose 3: KRP-104 100 mg	Experimental	Drug: KRP-104Tablet, once-daily for 24 weeks
Dose 4: KRP-104 20/120mg	Experimental	Drug: KRP-104Tablet, once-daily for 24 weeks (dose switch from 20 to 120 mg at week 12)
Placebo	Placebo comparator	Drug: PlaceboTablet, once-daily for 24 weeks

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Patients meeting the following criteria at the screening visit (Visit 1) will be eligible to participate in the trial:
Signed written informed consent;
Males and females 18 to 75 years of age, inclusive;
Females of childbearing potential must agree to use 2 adequate forms of barrier method contraception (eg, latex condom AND intrauterine device or a diaphragm) to avoid pregnancy while in the study;
On a stable dose (Greater than or equal to 10 weeks at the same dose) of metformin monotherapy (Less than or equal to 1500 mg/day or maximum tolerated dose), have an HbA1c greater than or equal to 7.0% and less than or equal to 10.5%; or

Key exclusion criteria (17 listed)

History of type 1 diabetes mellitus or history of diabetic ketoacidosis or persistent hypoglycemia;
History or presence of alcoholism or drug abuse within the 2 years prior to dosing;
Typical consumption of greater than or equal to 10 drinks of alcohol weekly;
Presence of any of the following conditions:
Fasting plasma glucose/blood glucose greater than 240 mg/dL (13.3 mmol/L) at Visit 3 (Week -2) (1 laboratory retest permitted);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KRP-104Tablet	Drug	Dose 1: KRP-104 40 mg, Dose 2: KRP-104 80 mg, Dose 3: KRP-104 100 mg, Dose 4: KRP-104 20/120mg
PlaceboTablet	Drug	Placebo

Primary outcome

Change in HbA1c From Baseline (Week 0) to Week 24
Time frame: Week 24
Mean Change in HbA1c (%) from Baseline to Week 24 with LOCF, ITT population LS mean (SE)

3 secondary outcomes

Change in Body Weight
Time frame: 24 weeks
Percentage of Patients Achieving HbA1c Less Than 7%
Time frame: 24 weeks
Percentage of Patients Requiring Rescue Therapy for Elevated Glucose
Time frame: 24 weeks of treatment.

Results and safety

Results posted to the registry on 26 Jun 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	81	70
Dose 1: KRP-104	81	74
Dose 2: KRP-104	80	73
Dose 3: KRP-104	81	76
Dose 4: KRP-104	80	75

Primary outcome: Change in HbA1c From Baseline (Week 0) to Week 24

Time frame: Week 24. Least squares mean (95% Confidence Interval). Unit: % HbA1c

Measure	Placebo n = 78	Dose 1: KRP-104 n = 79	Dose 2: KRP-104 n = 79	Dose 3: KRP-104 n = 80	Dose 4: KRP-104 n = 79
Value	-0.09 (0.097)	-0.41 (0)	-0.70 (-0.89 to -0.51)	-0.71 (-0.89 to -0.52)	-0.73 (-0.92 to -0.54)

Population analysed: Conducted analyses of ITT population of change in HbA1c from baseline (Week 0) to Week 24. If the Wk 24 measurement was missing, the last valid post-baseline observation (LOCF) algorithm was used to impute Week 24 value (1 on-treatment value required). Efficacy data collected after the initiation of rescue therapy was excluded from the analyses.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first site open on 19 October 2009 through 30 days after last subject out on 20 January 2011, approximately 1 year 5 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	3 of 81 (3.7%)	24 of 81 (29.6%)	Not reported
Dose 1: KRP-104	2 of 81 (2.5%)	16 of 81 (19.8%)	Not reported
Dose 2: KRP-104	4 of 80 (5%)	16 of 80 (20%)	Not reported
Dose 3: KRP-104	1 of 81 (1.2%)	17 of 81 (21%)	Not reported
Dose 4: KRP-104	1 of 80 (1.3%)	19 of 80 (23.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationPlotkin DJ, Lewin A, Logan D, Kato T, Kozarich J, Wei X, Vest J, Orloff D. KRP-104, A Uniquely Prandial-Targeted DPP-4 Inhibitor. Abstract and Poster # 822, Presented at: European Association for the Study of Diabetes 38th Annual Meeting, Berlin Germany, October 1-5, 2012.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Diane J Plotkin, PhD study director

ActivX Biosciences, Inc.

45 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KRP-104 in people with Type 2 Diabetes, run by ActivX Biosciences, Inc. at 45 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States, South Africa, Poland, Czechia, Russia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in HbA1c From Baseline (Week 0) to Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00995345, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2014.