Trial of DB289 for the Treatment of Stage I African Trypanosomiasis - Full Text View

Sponsors and Collaborators:	Immtech Pharmaceuticals, Inc Bill and Melinda Gates Foundation
Information provided by:	Immtech Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:	NCT00803933

Purpose

Human African Trypanosomiasis or sleeping sickness has made a spectacular return during the last decade, and in many places the demand largely surpasses the capacities of the treatment centers. Treatment of the disease remains unsatisfactory. All currently used drugs must be administered parenterally, treatment is lengthy, and adverse drug reactions frequent. There are currently no drugs that are easily administered and have low toxicity, and might thus be used as tools to support disease control.

This study aims to compare the safety and efficacy of DB289, a new, orally administered dication prodrug to pentamidine i.m. injection for the treatment of first stage sleeping sickness. The project will be executed in the framework of an international consortium consisting of several partners from academia, industry and from the Democratic Republic of Congo Ministries of Health.

Condition	Intervention	Phase
African Trypanosomiasis	Drug: DB289 Drug: Pentamidine	Phase II

Drug Information available for: Pentamidine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II b Trial of DB289 for the Treatment of Stage I African Trypanosomiasis

Further study details as provided by Immtech Pharmaceuticals, Inc:

Primary Outcome Measures:

The primary efficacy endpoint was the parasitological cure at 3 months after completion of treatment. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
The primary outcome measure for safety analysis was the rate of occurrence of Grade 3 or higher adverse events during the observation period. [ Time Frame: 12 day ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The secondary outcome measure was the incidence rate of adverse events (all Grades combined) during the 7- to 9-day observation period in Treatment Sequence 1 and during the 12-day observation period in Treatment Sequence 2. [ Time Frame: 12 day ] [ Designated as safety issue: Yes ]
The number and percentage of subjects with parasitological cure, subjects with confirmed (parasitological) treatment failure, and subjects with suspected treatment failure at 6, 12, and 24 months after completion of treatment. [ Time Frame: 6, 12, 24 months ] [ Designated as safety issue: No ]

Enrollment:	111
Study Start Date:	February 2003
Study Completion Date:	June 2005
Primary Completion Date:	February 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
DB289: Experimental Pafuramidine maleate (DB289), 100 mg BID orally	Drug: DB289 Pafuramidine maleate (DB289), 100 mg BID orally
Pentamidine: Active Comparator Pentamidine isethionate (Aventis) for injection (200 mg/vial), 4 mg/kg QD IM	Drug: Pentamidine Pentamidine isethionate (Aventis) for injection (200 mg/vial), 4 mg/kg QD IM

Eligibility

Ages Eligible for Study:	15 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The patient has early stage T. b. gambiense infection i.e. parasitologically confirmed infection in the blood or lymph node aspirate and greater than or equal to 5 WBC mm-3 detected in the CSF by microscopic examination
Patient is 15 to 50 years old
Patient has a minimal weight of 35 kilograms
If the patient is female of child bearing potential (a women will be considered of non-child bearing potential only if she has been post menopausal for over 2 years or has had a hysterectomy):
1. she is not lactating,
2. she had a negative urine pregnancy test result within 24 hours prior to DB289 treatment and
3. she agrees to use a medically proven method of contraception (abstinence from sexual intercourse is an acceptable method) from the day of consent on until the end of the observation period (day 7).
Patient has understood and signed the Informed Consent. If the patient is minor, a legal guardian has signed the Informed Consent

Exclusion Criteria:

The patient has late stage T.b. gambiense infection i.e. presence of parasite in the CSF upon microscopic examination or a WBC count of > 5mm-1
Active clinically relevant medical conditions that in the Investigator opinion may jeopardize subject safety or interfere with participation in the study, including but not limited to: significant liver diseases, chronic pulmonary diseases, significant cardiovascular diseases, diabetes, thyroid diseases, gout, infection including known HIV infection, CNS trauma or seizure disorders (A list of typical signs and symptoms is provided for guidance of the investigator in attachment 1)
Coma Score of less than 9 on the Glasgow Coma Scale (Appendix 8)
Withdrawal of consent at any time during the study
Any condition which compromises ability to communicate with the investigator as required for the completion of this study.
The subject has been previously treated for African Trypanosomiasis.
The subject has been previously enrolled in the study. -

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00803933

Locations

Congo, Kinshasa
CDTC Maluku
Gombe, Kinshasa, Congo
Vanga Hospital
Gombe, Kinshasa, Congo

Sponsors and Collaborators

Immtech Pharmaceuticals, Inc

Bill and Melinda Gates Foundation

Investigators

Principal Investigator:

Victor Kande, MD

Programme Nationale de Lutte contre la Trypanosomiase Humaine Africaine

More Information

Responsible Party:	Swiss Tropical Institute ( Christian Burri, Study Director )
Study ID Numbers:	289-C-006
Study First Received:	December 4, 2008
Last Updated:	December 5, 2008
ClinicalTrials.gov Identifier:	NCT00803933
Health Authority:	United States: Food and Drug Administration

Keywords provided by Immtech Pharmaceuticals, Inc:

first stage
Trypanosoma brucei gambiense
T. b. gambiense
sleeping sickness
First stage T. b. gambiense sleeping sickness

Study placed in the following topic categories:

Protozoan Infections
Clotrimazole
Miconazole
Tioconazole
Trypanosomiasis, African

Trypanosomiasis
Pentamidine
Parasitic Diseases
African trypanosomiasis

Additional relevant MeSH terms:

Trypanocidal Agents
Anti-Infective Agents
Antiparasitic Agents
Antiprotozoal Agents
Therapeutic Uses

Antifungal Agents
Sarcomastigophora Infections
Mastigophora Infections
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009